5-MeO-DMT

5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, as well as O-methylbufotenin or mebufotenin, is a naturally occurring psychedelic of the tryptamine family.<ref name="ErmakovaDunbarRucker2022">Template:Cite journal</ref><ref name="ReckwegUthaugSzabo2022">Template:Cite journal</ref><ref name="DourronNicholsSimonsson2023">Template:Cite journal</ref><ref name="ShenJiangWinter2010">Template:Cite journal</ref> 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.<ref name="ErmakovaDunbarRucker2022" /> It may occur naturally in humans as well.<ref name="ErmakovaDunbarRucker2022" /> Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America.<ref name="ErmakovaDunbarRucker2022" /><ref name="AraújoCarvalhoBastos2015">Template:Cite journal</ref> Slang terms include five-methoxy, the power, bufo, and toad venom.<ref>Template:Cite web</ref> The drug has been described as the most powerful psychedelic<ref name="LindenRobin2023">Template:Cite book</ref><ref name="Delgrasso2024" /> and, by journalist Michael Pollan, as the "Mount Everest of psychedelics".<ref name="Delgrasso2024" /><ref name="Hayes2025">Template:Cite journal</ref>

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.<ref name="Hayes2025" /> The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT_1A and 5-HT_2A receptors, among others.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="HolzeSinghLiechti2024">Template:Cite journal</ref> However, 5-MeO-DMT differs from most other serotonergic psychedelics in having 100- to 1,000-fold higher affinity for the serotonin 5-HT_1A receptor over the serotonin 5-HT_2A receptor.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="HolzeSinghLiechti2024" /> 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.<ref name="ErmakovaDunbarRucker2022" /><ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /> Nonetheless, 5-MeO-DMT reliably produces mystical experiences in most people who take it.<ref name="Hayes2025" /> Like DMT, 5-MeO-DMT is only active non-orally and has a very rapid onset of action and short duration.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /> However, 5-MeO-DMT is 4- to 20-fold more potent than DMT in humans.<ref name="ShenJiangWinter2010" /><ref name="Hayes2025" />

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.<ref name="Delgrasso2024" /><ref name="ErmakovaDunbarRucker2022" /> The use of 5-MeO-DMT-containing toad venom was first described in 1984.<ref name="Delgrasso2024" /><ref name="WeilDavis1994" /> It is a controlled substance in some countries, for instance the United States, United Kingdom, Australia, and New Zealand.<ref name="ErmakovaDunbarRucker2022" /> The drug is used recreationally and several deaths have been reported in association with its use.<ref name="ErmakovaDunbarRucker2022" /><ref name="MalacaLoFaroTamborra2020">Template:Cite journal</ref> 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).<ref name="Hayes2025" /><ref name="SextonNicholsHendricks2019">Template:Cite journal</ref> 5-MeO-DMT is being developed for potential use in medicine in the treatment of neuropsychiatric disorders such as depression.<ref name="Hayes_2025">Template:Cite journal</ref><ref name="ErmakovaDunbarRucker2022" /><ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" />

Uses

Recreational

5-MeO-DMT is used as a recreational drug.<ref name="ReckwegUthaugSzabo2022" /><ref name="ErmakovaDunbarRucker2022" /><ref name="TiHKAL" /> It is not orally active, requiring a parenteral route such as smoking to produce effects.<ref name="ReckwegUthaugSzabo2022" /><ref name="ErmakovaDunbarRucker2022" /><ref name="TiHKAL" /> Other parenteral routes such as intravenous injection, intramuscular injection, rectal administration, sublingual administration, or intranasal administration have also less commonly been used.<ref name="ReckwegUthaugSzabo2022" /><ref name="ErmakovaDunbarRucker2022" /><ref name="TiHKAL" />

In addition to parenteral 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.<ref name="TiHKAL-Harmaline">Template:Cite web</ref> However, combination of 5-MeO-DMT with MAOIs can also result in accidental overdose, including instances of serotonin syndrome and death.<ref name="ShenJiangWinter2010" />

Medical

Preliminary clinical findings suggest that 5-MeO-DMT might have antidepressant and anxiolytic effects.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Religious

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.<ref>Template:Cite book</ref><ref name="Erowid">Template:Cite web</ref> 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.<ref name="Erowid"/>Template:Unreliable source?

Dosing

5-MeO-DMT has been described as having a steep dose–response curve.<ref name="Hayes2025" />

Effects

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.<ref>5-MeO-DMT - PsychonautWiki</ref> 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.<ref>Template:Cite web</ref>Template:Better source needed

The subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics.<ref name="DourronNicholsSimonsson2023" /><ref name="ErmakovaDunbarRucker2022" /><ref name="Hayes2025" /> 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".<ref name="DourronNicholsSimonsson2023" /><ref name="ErmakovaDunbarRucker2022" /><ref name="Hayes2025" /> These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void or amnesia of the experience.<ref name="DourronNicholsSimonsson2023" /><ref name="ErmakovaDunbarRucker2022" /><ref name="Hayes2025" /> 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".<ref name="DourronNicholsSimonsson2023" /><ref name="Hayes2025" /> As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound, spiritual, religious, and/or mystical.<ref name="DourronNicholsSimonsson2023" /><ref name="ErmakovaDunbarRucker2022" /><ref name="Hayes2025" />

The experiences of 5-MeO-DMT have been related to the experience of ecstatic seizures.<ref name="DourronNicholsSimonsson2023" />

Pharmacology

Pharmacodynamics

Template:Nowrap

Target	Affinity (Ki, nM)
5-HT1A	1.9–28 (Ki) 3.92–1,060 (Template:Abbrlink) 68–98% (Template:Abbrlink)
5-HT1B	14–351 (Ki) 1.53 (Template:Abbr) 78% (Template:Abbr)
5-HT1D	2.3–20 (Ki) 37 (Template:Abbr) 98% (Template:Abbr)
5-HT1E	360–528 (Ki) 92–160 (Template:Abbr) 119% (Template:Abbr)
5-HT1F	37 (Ki) 14 (Template:Abbr) 93% (Template:Abbr)
5-HT2A	15–2,011 (Ki) 1.76–784 (Template:Abbr) 82–106% (Template:Abbr)
5-HT2B	19–3,884 (Ki) 5.9–30 (Template:Abbr) 21–73% (Template:Abbr)
5-HT2C	42–538 (Ki) 10–31 (Template:Abbr) 84–90% (Template:Abbr)
5-HT3	>10,000
5-HT4	>10,000 (Template:Abbr)
5-HT5A	277–505 (Ki) 110 (Template:Abbr) 107% (Template:Abbr)
5-HT6	6.5–78 (Ki) 0.24 (Template:Abbr) 125% (Template:Abbr)
5-HT7	3.9–30 (Ki) 65.7 (Template:Abbr) 107% (Template:Abbr)
MT1	210 (Ki) 257 (Template:Abbr)
MT2	16 (Ki) 112 (Template:Abbr)
α1A	4,373–>10,000
α1B	2,188–>10,000
α1D	Template:Abbr
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
Template:Abbrlink	2,032–>10,000 (Ki) 2,184–>10,000 ([[IC50|Template:Abbr)]] >10,000 (Template:Abbr)
Template:Abbrlink	2,859–>10,000 (Ki) >10,000 (Template:Abbr) >10,000 (Template:Abbr)
Template:Abbrlink	>10,000 (Ki) >10,000 (Template:Abbr) >10,000 (Template:Abbr)
Notes: The smaller the value, the more avidly the drug binds to the site. Proteins are mostly but not exclusively human. Refs:<ref name="ErmakovaDunbarRucker2022" /><ref name="HolzeSinghLiechti2024" /><ref name="Ray2010">Template:Cite journal</ref><ref name="CameronTombariLu2021">Template:Cite journal</ref><ref name="HalberstadtNicholsGeyer2012">Template:Cite journal</ref><ref name="delaFuenteRevengaFernández-SáezHerrera-Arozamena2015">Template:Cite journal</ref><ref name="BloughLandavazoDecker2014" /><ref name="JayakodiarachchiMaurerSchultz2024" /><ref name="US11440879">Template:Cite patent</ref><ref name="ChenLiYu2023a">Template:Cite journal</ref><ref name="ChenLiYu2023b">Template:Citation</ref><ref name="PDSPKiDatabase">Template:Cite web</ref><ref name="BindingDB">Template:Cite web</ref><ref name="Puigseslloses_2024" />

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-HT_2A receptors, 5-MeO-DMT shows 1,000-fold greater affinity for the serotonin 5-HT_1A receptor over the serotonin 5-HT_2A receptor.<ref name="Ray2010" /> In line with its affinity for serotonin 5-HT_1A receptors, 5-MeO-DMT is extremely potent at suppressing the firing of dorsal raphe nucleus serotonin neurons.<ref>Template:Cite journal</ref> Further, its activity in rats was attenuated with the selective serotonin 5-HT_1A receptor antagonist WAY-100635, while selective serotonin 5-HT_2A receptor antagonist volinanserin failed to demonstrate any change.<ref>Template:Cite journal</ref> Additional mechanisms of action such as inhibition of monoamine reuptake may also be involved in its effects.<ref>Template:Cite journal</ref>

Similarly to other serotonergic psychedelics, 5-MeO-DMT is a non-selective serotonin receptor agonist, including of the serotonin 5-HT_1A, 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors, among others.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="JayakodiarachchiMaurerSchultz2024">Template:Cite journal</ref><ref name="BloughLandavazoDecker2014" /><ref name="Puigseslloses_2024">Template:Cite journal</ref> It is 4- to 10-fold more potent as a hallucinogen than DMT in humans.<ref name="ShenJiangWinter2010" /> 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-HT_2A receptor.<ref name="DourronNicholsSimonsson2023" /> In any case, 5-MeO-DMT does still activate the serotonin 5-HT_2A receptor and does still produce psychedelic effects.<ref name="DourronNicholsSimonsson2023" /> It has been proposed that 5-MeO-DMT be considered an "atypical" psychedelic.<ref name="DourronNicholsSimonsson2023" /> This relates to the fact that 5-MeO-DMT has 100- to 1,000-fold selectivity for the serotonin 5-HT_1A receptor over the serotonin 5-HT_2A receptor and that the actions of 5-MeO-DMT appear to be primarily mediated by serotonin 5-HT_1A receptor activation.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="ShenJiangWinter2010" /><ref name="HolzeSinghLiechti2024" /> For example, the potencies of drugs substituting for 5-MeO-DMT in drug discrimination assays is well-correlated with their serotonin 5-HT_1A receptor affinities, and the discriminative stimulus effects of 5-MeO-DMT are attenuated by serotonin 5-HT_1A receptor antagonists.<ref name="ShenJiangWinter2010" /> However, there is partial generalization of 5-MeO-DMT to the selective serotonin 5-HT₂ receptor agonist (–)-DOM in animals.<ref name="ShenJiangWinter2010" /> 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.<ref name="DourronNicholsSimonsson2023" />

Although 5-MeO-DMT shows dramatically higher affinity for the serotonin 5-HT_1A receptor than for the serotonin 5-HT_2A receptor, the situation appears to be very different in terms of its actual activational potencies at these receptors.<ref name="CummingScheideggerDornbierer2021">Template:Cite journal</ref><ref name="BloughLandavazoDecker2014" /><ref name="CameronTombariLu2021" /> Its Template:Abbrlink values have been found to be 1.80 to 3.87Template:NbspnM at the serotonin 5-HT_2A receptor and 3.92 to 1,060Template:NbspnM at the serotonin 5-HT_1A receptor.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" /><ref name="CameronTombariLu2021" /><ref name="BindingDB" /> For comparison, the Template:Abbr values of DMT were found to be 38.3Template:NbspnM at the serotonin 5-HT_2A receptor and >10,000Template:NbspnM at the serotonin 5-HT_1A receptor in one of the same studies.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" /> Hence, 5-MeO-DMT appears to be similarly potent or as much as 200-fold more potent as an agonist of the serotonin 5-HT_2A receptor than of the serotonin 5-HT_1A receptor.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" /><ref name="CameronTombariLu2021" /> In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT_2A receptor.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" />

Besides the serotonin receptors, 5-MeO-DMT is an agonist of the melatonin MT₁ and MT₂ receptors.<ref name="delaFuenteRevengaFernández-SáezHerrera-Arozamena2015" /><ref name="BindingDB" /><ref name="PDSPKiDatabase" /> Unlike DMT, 5-MeO-DMT is not a ligand or agonist of the sigma receptors.<ref name="ErmakovaDunbarRucker2022" /><ref name="BindingDB" /><ref name="PDSPKiDatabase" /> In contrast to certain other tryptamines, 5-MeO-DMT is inactive as a monoamine releasing agent, including of serotonin, norepinephrine, and dopamine.<ref name="BloughLandavazoDecker2014" /> However, it is a weak serotonin reuptake inhibitor, with an Template:Abbrlink value of 2,184Template:NbspnM.<ref name="BloughLandavazoDecker2014" /> Conversely, it is inactive as a dopamine and norepinephrine reuptake inhibitor (Template:Abbr = >10,000Template:NbspnM).<ref name="BloughLandavazoDecker2014" />

Similarly to DMT, but in contrast to most other psychedelics, like LSD and psilocybin,<ref name="Halberstadt2015">Template:Cite journal</ref><ref name="JiménezBouso2022">Template:Cite journal</ref> there appears to be very little development of tolerance with 5-MeO-DMT.<ref name="ErmakovaDunbarRucker2022" /><ref name="BloughLandavazoDecker2014">Template:Cite journal</ref><ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /> In fact, there may even be sensitization to the effects of 5-MeO-DMT.<ref name="DourronNicholsSimonsson2023" /> The lack of tolerance development with 5-MeO-DMT may be due to biased agonism of the serotonin 5-HT_2A receptor.<ref name="ErmakovaDunbarRucker2022" /> More specifically, 5-MeO-DMT activates the G_q signaling pathway of the serotonin 5-HT_2A receptor with much less potency in recruiting β-arrestin2.<ref name="ErmakovaDunbarRucker2022" /><ref name="BloughLandavazoDecker2014" /> Activation of β-arrestin2 is linked to receptor downregulation and tachyphylaxis.<ref name="JiménezBouso2022" /><ref name="BarksdaleDossFonzo2024">Template:Cite journal</ref><ref name="WallachCaoCalkins2023">Template:Cite journal</ref>

Pharmacokinetics

Absorption

5-MeO-DMT is not orally active and must be administered parenterally.<ref name="TiHKAL" />

Distribution

5-MeO-DMT is lipophilic and is thought to easily cross the blood–brain barrier.<ref name="ShenJiangWinter2010" /> Accordingly, 5-MeO-DMT readily accumulates in the brain in animals with levels higher than in blood.<ref name="ShenJiangWinter2010" /> 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.<ref name="ShenJiangWinter2010" /><ref name="PlazasFaraone2023">Template:Cite journal</ref><ref name="McBride2000">Template:Cite journal</ref>

Metabolism

Bufotenin is an active metabolite of 5-MeO-DMT, formed by O-demethylation by cytochrome P450 CYP2D6.<ref name="ShenJiangWinter2010" /> Bufotenin notably has much higher affinity for the serotonin 5-HT_2A receptor than 5-MeO-DMT itself.<ref name="ShenJiangWinter2010" /> However, bufotenin does not seem to be extensively produced from 5-MeO-DMT in the brain.<ref name="ShenJiangWinter2010" /> 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.<ref name="ShenJiangWinter2010" /> Hence, the involvement of bufotenin in the psychoactive effects of 5-MeO-DMT is uncertain.<ref name="ShenJiangWinter2010" />

The metabolism of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by monoamine oxidase inhibitors (MAOIs).<ref name="ShenJiangWinter2010" /> In addition, MAOIs allow 5-MeO-DMT to become orally active in humans.<ref name="ShenJiangWinter2010" /> Combining 5-MeO-DMT with MAOIs has sometimes resulted in serotonin syndrome and death in humans.<ref name="ShenJiangWinter2010" />

Elimination

The elimination half-life of 5-MeO-DMT, administered sublingually, was found to be 28Template:Nbspminutes.<ref name="BistueMillónNogueraBruno2025" />

Chemistry

5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, is a substituted tryptamine derivative. <ref name="TiHKAL" />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).<ref name="TiHKAL" />

Properties

5-MeO-DMT has a relatively high experimental log P of 3.30.<ref name="ShenJiangWinter2010" /><ref name="McBride2000" />

Synthesis

The chemical synthesis of 5-MeO-DMT has been described.<ref name="TiHKAL" /><ref name="SherwoodClaveauLancelotta2020">Template:Cite journal</ref><ref>Template:Cite web</ref>

Analogues and derivatives

Analogues of 5-MeO-DMT include 5-MeO-MALT, 4-MeO-DMT, 5-MeO-AMT, 5-MeO-DET, 5-MeO-DPT, 5-MeO-DIPT, 5-MeO-MiPT, 5-EtO-DMT, 5-MeO-MET, and 5-MeO-pyr-T.<ref name="TiHKAL" /> Other analogues include dimemebfe and EMDT.<ref name="TiHKAL" />

Natural occurrence

Plants

Plant sources

Family	Plants
Rutaceae	Dictyoloma incanescens,<ref>Template:Cite journal</ref> Limonia acidissima,<ref name="bluezoo_tryptamines">Template:Cite web</ref> Melicope leptococca<ref name="erowid_tryptamines">Template:Cite web</ref>
Fabaceae	Anadenanthera peregrina,<ref name="trout_notes">Template:Cite web</ref> Acacia auriculiformis,<ref name="trout_notes" /> Acacia victoriae,<ref name="trout_notes" /> Desmodium gangeticum,<ref name="trout_notes" /> Lespedeza bicolor,<ref name="erowid_tryptamines" /><ref name="bluezoo_tryptamines" /> Mimosa pudica,<ref name="trout_notes" /> Mucuna pruriens,<ref name="bluezoo_tryptamines" /><ref name="erowid_tryptamines" /> Phyllodium pulchellum<ref name="bluezoo_tryptamines" /><ref name="erowid_tryptamines" />
Poaceae	Phalaris tuberosa<ref name="trout_notes" />
Malpighiaceae	Diplopterys cabrerana<ref name="forensic_chemistry" />
Cactaceae	Echinocereus salm-dyckianus,<ref name="bluezoo_tryptamines" /> Echinocereus triglochidiatus<ref name="bluezoo_tryptamines" />
Myristicaceae	Horsfieldia superba,<ref name="bluezoo_tryptamines" /> Iryanthera macrophylla,<ref name="bluezoo_tryptamines" /> Osteophloeum platyspermum,<ref name="forensic_chemistry" /> Virola theiodora,<ref name="bluezoo_tryptamines"/> V. calophylla,<ref name="forensic_chemistry" /> V. multinervia,<ref name="forensic_chemistry" /> V. peruviana,<ref name="forensic_chemistry" /> V. rufula,<ref name="forensic_chemistry" /> V. venosa<ref name="forensic_chemistry" />

Toads

Colorado River toad

Animal Sources

Family	Animals
Bufonidae	Colorado River toad (Incilius alvarius)<ref>Template:Cite web</ref><ref name=pmid30982127/><ref name="erowid_tryptamines" />

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.<ref>Template:Cite web</ref> The smoking of I. alvarius secretions should not be confused with the urban legend of toad licking.<ref name="TiHKAL">Template:Cite web</ref> Since 1983, the animal has become a popular source of 5-MeO-DMT for recreational or spiritual purposes.<ref>Template:Cite news</ref> Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.<ref>Template:Cite web</ref> 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.<ref>Template:Cite book</ref>

Fungi

Fungal Sources

Family	Fungi
Amanitaceae	Amanita citrina,<ref name="forensic_chemistry">Template:Cite book</ref> Amanita porphyria<ref name="forensic_chemistry" />

History

5-MeO-DMT was first synthesized by Toshio Hoshino in 1935.<ref name="Delgrasso2024">Template:Cite journal</ref><ref name="ErmakovaDunbarRucker2022" /><ref name="HoshinoShimodaira1936">Template:Cite journal</ref> It was isolated from the flowering plant Dictyoloma incanescens in 1959.<ref name="ErmakovaDunbarRucker2022" /><ref name="PachterZachariasRibeiro1959">Template:Cite journal</ref> The drug was subsequently isolated from numerous other plant, fungal, and animal sources over time.<ref name="Delgrasso2024" /><ref name="ErmakovaDunbarRucker2022" /> The behavioral effects of 5-MeO-DMT in animals were first reported by 1961.<ref name="BrimblecombePinder1975">Template:Cite book</ref><ref name="GessnerGodseKrull1968">Template:Cite journal</ref><ref name="GessnerMcIsaacPage1961">Template:Cite journal</ref><ref name="GessnerIrvine1962">Template:Cite journal</ref><ref name="GallagherKochMoore1964">Template:Cite journal</ref> 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.<ref name="BrimblecombePinder1975" /><ref name="Shulgin1976" /><ref name="GessnerGodseKrull1968" /><ref name="Holmstedt1965">Template:Cite journal</ref> 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.<ref name="Delgrasso2024" /><ref name="ErmakovaDunbarRucker2022" /><ref name="ErspamerVitaliRoseghini1965">Template:Cite journal</ref><ref name="EspamerVitaliRoseghini1967">Template:Cite journal</ref>

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.<ref name="BrimblecombePinder1975" /><ref name="Shulgin1976">Template:Cite book</ref><ref name="Shulgin1970">Template:Cite book</ref><ref>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."</ref><ref name="deSmet1983">Template:Cite journal</ref><ref name="TiHKAL" /> 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.<ref name="Delgrasso2024" /> Subsequently, Andrew Weil and Wade Davis, in part citing the pamphlet, described the psychoactive effects of the toad in the scientific literature in 1992.<ref name="WeilDavis1994">Template:Cite journal</ref><ref name="DavisWeil1992">Template:Cite journal</ref> In addition, they described the finding as the first instance of a psychedelic from an animal source to be discovered.<ref name="WeilDavis1994" /> Recreational use of the toads, beyond the pamphlet, was encountered by the late 1980s and became a media sensation.<ref name="Lyttle1993">Template:Cite journal</ref> 5-MeO-DMT became a controlled substance in the United States in 2009.<ref name="ErmakovaDunbarRucker2022" />

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 Template:Abbrlink. Other names can include O-methylbufotenin, O-methyl-5-HO-DMT, and O,N,N-trimethylserotonin.

Legal status

Australia

As a structural analog of N,N-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.<ref>Template:Cite web</ref>

Canada

5-MeO-DMT is legal for personal use and possession in Canada,<ref>Template:Cite web</ref> though sale, distribution, and other activities involving the substance are illegal under Canadian federal law.

China

As of October 2015, 5-MeO-DMT is a controlled substance in China.<ref>Template:Cite web</ref>

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.<ref>Template:Cite web</ref>

Turkey

5-MeO-DMT has been controlled in Turkey since December 2013.<ref>Template:Cite web</ref>

United States

5-MeO-DMT was made a Schedule I controlled substance in January 2011.<ref>Template:Cite journal</ref>

Research

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).<ref name=pmid30982127>Template:Cite journal</ref> A 2018 study found that a single dose of 5-MeO-DMT induced neurogenesis in mice.<ref>Template:Cite journal</ref>

Depression

5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with treatment-resistant depression (TRD).<ref>Template:Cite web</ref> Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers<ref>Template:Cite journal</ref> 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.<ref name="ReckwegvanLeeuwenHenquet2023">Template:Cite journal</ref><ref>Template:Cite press release</ref> 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.<ref>Template:Cite press release</ref>

In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients with treatment-resistant depression (TRD).<ref name="GHResearch2025" /> 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.<ref name="GHResearch2025" /> The trial also met all secondary endpoints, and the treatment was well-tolerated with no serious adverse events reported.<ref name="GHResearch2025">Template:Cite news</ref>

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.<ref>Template:Cite web</ref><ref>Template:Cite press release</ref> 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."<ref>Template:Cite news</ref>

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.<ref name="Ramaekers2025">Template:Cite journal</ref><ref name="RamaekersReckwegMason2025">Template:Cite journal</ref>

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.<ref name="Hayes2025" />

See also

• Substituted tryptamine
• Hamilton's Pharmacopeia
• List of entheogens
• Psychoplastogen

External links

• 5-MeO-DMT - Isomer Design
• 5-MeO-DMT - PsychonautWiki
• 5-MeO-DMT - Erowid
• 5-MeO-DMT - TiHKAL - Erowid
• 5-MeO-DMT - TiHKAL - Isomer Design
• 5-MeO-DMT: Unpacking The Mysteries of This Powerful Psychedelic - Tripsitter