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| Other names | 5-Methoxy-N,N-dimethyltryptamine; 5-Methoxy-N,N-DMT; 5-MeO-DMT; 5-OMe-DMT; MDMT;O-Methylbufotenin; Mebufotenin; Methylbufotenin;N,N,O-Trimethylserotonin; CT-4334; BPL-002; BPL-003; LSR-1019 |
| Routes of administration | Inhalation,insufflation,sublingual,intramuscular,intravenous,oral (with anMAOITooltip monoamine oxidase inhibitor)[1][2][3] |
| Drug class | Serotonergic psychedelic (hallucinogen) |
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| Bioavailability | Oral: inactive (without anMAOITooltip monoamine oxidase inhibitor) or weak[1][2] |
| Metabolism | Oxidative deamination (MAOTooltip monoamine oxidase),O-demethylation (CYP2D6)[2][1][5] |
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| ECHA InfoCard | 100.012.558 |
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| Formula | C13H18N2O |
| Molar mass | 218.300 g·mol−1 |
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5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known asO-methylbufotenin ormebufotenin (INNTooltip International Nonproprietary Name), is anaturally occurringpsychedelic of thetryptamine family.[6][1][5][2] It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, theColorado River toad.[6] It may occur naturally in humans as well.[6] Like its close relativesdimethyltryptamine (DMT) andbufotenin (5-HO-DMT), it has been used as anentheogen inSouth America.[6][8] Slang terms includefive-methoxy,the power,bufo, andtoad venom.[9] The drug has been described as the most powerful psychedelic[10][11] and, by journalistMichael Pollan, as the "Mount Everest of psychedelics".[11][12]
Adverse effects of 5-MeO-DMT includesickness,vomiting,headache,chest pressure,fatigue,anxiety,fear,terror,confusion,paranoia,crying, loss ofawareness andmotor control, andreactivations.[12] The drug acts as anon-selectiveserotonin receptor agonist, including of theserotonin5-HT1A and5-HT2A receptors, among others.[1][5][13] However, 5-MeO-DMT differs from most other serotonergic psychedelics in having 100- to 1,000-fold higheraffinity for the serotonin 5-HT1A receptor over the serotonin 5-HT2A receptor.[1][5][13] 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.[6][1][5] Nonetheless, 5-MeO-DMT reliably producesmystical experiences in most people who take it.[12] Like DMT, 5-MeO-DMT is only activenon-orally and has a very rapidonset of action and shortduration.[1][5] However, 5-MeO-DMT is 4- to 20-fold morepotent than DMT in humans.[2][12]
5-MeO-DMT was first described by 1936, was firstisolated fromnatural sources by 1959, and was first reported to be hallucinogenic by 1970.[11][6] The use of 5-MeO-DMT-containing toad venom was first described in 1984.[11][14] It is acontrolled substance in some countries, for instance theUnited States,United Kingdom,Australia, andNew Zealand.[6] The drug is usedrecreationally and several deaths have been reported in association with its use.[6][15] Use of 5-MeO-DMT is rare compared with other psychedelics, with only 0.003% of the United States general population having reported taking it in 2019 (compared to 8.5% forpsilocybin).[12][16] 5-MeO-DMT is being developed for potential use in medicine in the treatment ofneuropsychiatric disorders such asdepression.[17][6][1][5]
5-MeO-DMT is used as arecreational drug.
Preliminary clinical findings suggest that 5-MeO-DMT might haveantidepressant andanxiolytic effects.[18][19]
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.[20][21] Between 1970 and 1990, smoking of 5-MeO-DMT onparsley was probably one of the two most common forms ofingestion in theUnited States.[21][unreliable source?]
5-MeO-DMT has been described as having a steepdose–response curve.[12]
When smoked, the duration of the effects of 5-MeO-DMT can be as little as ten minutes; wheninsufflated, up to two hours, although the peak effects are usually in the range of 10–40 minutes.[22] Effects vary and can range from radical perspective shifting and perception of new insights, euphoria, immersive experiences,dissociation and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, panic, andego death.[23][better source needed]
The subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics.[5][6][12] Whereas DMT is described as producing more "information-rich" experiences, with "rich sensory phenomenology", visuals, and experiences of encountering entities and visiting other worlds, 5-MeO-DMT is described as having a relative lack of visual effects, producing a sense of "nothingness", and causing experiences that are said to be "content-free" and sometimes known as "whiteouts".[5][6][12] These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void oramnesia of the experience.[5][6][12] In spite of this however, some have described the experiences asorgasmic,ecstatic, andblissful, whereas others have described them as terror or "information overwhelm".[5][12] As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound, spiritual, religious, and/or mystical.[5][6][12]
The experiences of 5-MeO-DMT have been related to the experience ofecstatic seizures.[5]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 1.9–28 (Ki) 3.92–1,060 (EC50Tooltip half-maximal effective concentration) 68–98% (EmaxTooltip maximal efficacy) |
| 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 | 36–3,884 (Ki) 5.87–30.1 (EC50) 21–73% (Emax) |
| 5-HT2C | 42–538 (Ki) 10.1–31 (EC50) 84–90% (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 | 938–1,890 |
| α2B | 430–2,640 |
| α2C | 206–508 |
| 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 | 3,120–>10,000 |
| D5 | >10,000 |
| H1 | 7,580 |
| H2–H4 | >10,000 |
| M1–M5 | >10,000 |
| σ1 | >10,000 |
| σ2 | >10,000 |
| SERTTooltip Serotonin transporter | 2,032–3,603 (Ki) 2,184–7,020 (IC50) >10,000 (EC50) |
| NETTooltip Norepinephrine transporter | 2,859–>10,000 (Ki) >10,000 (IC50) >10,000 (EC50) |
| DATTooltip Dopamine transporter | >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:[6][13][24][25][26][27] | |
5-MeO-DMT is amethoxylatedderivative ofdimethyltryptamine (DMT). While most common psychedelics are believed to primarily elicit psychological effects throughagonism ofserotonin5-HT2A receptors, 5-MeO-DMT shows 1,000-fold greateraffinity for the serotonin5-HT1A receptor over the serotonin 5-HT2A receptor.[24] In line with its affinity for serotonin 5-HT1A receptors, 5-MeO-DMT is extremelypotent at suppressing the firing ofdorsal raphe nucleus serotoninneurons.[35] Further, its activity in rats was attenuated with theselective serotonin 5-HT1A receptorantagonistWAY-100635, while selective serotonin 5-HT2A receptor antagonistvolinanserin failed to demonstrate any change.[36] Additionalmechanisms of action such asinhibition ofmonoaminereuptake may also be involved in its effects.[37]
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][29][28] 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][13] 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.[38][28][25] ItsEC50Tooltip half-maximal effective concentration 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.[38][28][25][34] For comparison, theEC50 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.[38][28] Hence, 5-MeO-DMT appears to be similarly potent or as much as 200-fold more potent as an agonist of the serotonin 5-HT2A receptor than of the serotonin 5-HT1A receptor.[38][28][25] In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT2A receptor.[38][28]
Besides the serotonin receptors, 5-MeO-DMT is anagonist of themelatoninMT1 andMT2 receptors.[27][34][33] Unlike DMT, 5-MeO-DMT is not aligand or agonist of thesigma receptors.[6][34][33] In contrast to certain other tryptamines, 5-MeO-DMT is inactive as amonoamine releasing agent, including ofserotonin,norepinephrine, anddopamine.[28] However, it is a weakserotonin reuptake inhibitor, with anIC50Tooltip half-maximal inhibitory concentration value of 2,184 nM.[28] Conversely, it is inactive as adopamine andnorepinephrine reuptake inhibitor (IC50 = >10,000 nM).[28]
Similarly to DMT, but in contrast to most other psychedelics, like LSD and psilocybin,[39][40] there appears to be very little development oftolerance with 5-MeO-DMT.[6][28][1][5] In fact, there may even besensitization to the effects of 5-MeO-DMT.[5] The lack of tolerance development with 5-MeO-DMT may be due tobiased agonism of the serotonin 5-HT2A receptor.[6] More specifically, 5-MeO-DMT activates theGqsignaling pathway of the serotonin 5-HT2A receptor with much lesspotency in recruitingβ-arrestin2.[6][28] Activation of β-arrestin2 is linked toreceptor downregulation andtachyphylaxis.[40][41][42]
5-MeO-DMT islipophilic and is thought to easily cross theblood–brain barrier.[2] Accordingly, 5-MeO-DMT readily accumulates in the brain in animals with levels higher than in blood.[2] This is in notable contrast tobufotenin (5-HO-DMT orN,N-dimethylserotonin) andserotonin (5-HT), which arehydrophilic and have varying degrees ofperipheral selectivity.[2][43][44]
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]
Theelimination half-life of 5-MeO-DMT, administeredsublingually, was found to be 28 minutes.[7]
5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, is asubstituted tryptaminederivative. It is the 5-methoxylated derivative ofN,N-dimethyltryptamine (DMT), theN,N-dimethylated derivative of5-methoxytryptamine (5-MT; mexamine), and theO-methylated derivative ofbufotenin (5-HO-DMT).
It has a relatively high experimentallog P of 3.30.[2][44]
In addition to occurring naturally, 5-MeO-DMT can be produced synthetically.[45][46]
Analogues of 5-MeO-DMT include5-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, and5-MeO-pyr-T. Other analogues includedimemebfe andEMDT.
| Family | Animals |
|---|---|
| Bufonidae | Colorado River toad (Incilius alvarius)[52][53][49] |
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.[54] 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.[55] Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.[56] Concerned with the ecological impacts of the growing use 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.[57]
| Family | Fungi |
|---|---|
| Amanitaceae | Amanita citrina,[51]Amanita porphyria[51] |
5-MeO-DMT was firstsynthesized byToshio Hoshino in 1935.[11][6][58] It wasisolated from theflowering plantDictyoloma incanescens in 1959.[6][59] The drug was subsequently isolated from numerous otherplant,fungal, andanimalsources over time.[11][6] The behavioral effects of 5-MeO-DMT in animals were first reported by 1961.[60][61][62][63][64] In 1965, 5-MeO-DMT was reported to be the main component of thehallucinogenic snuff known variously as parica, epena, or yakee that is prepared and used from theresin of theVirola theiodora tree by indigenous people in NorthernSouth America.[60][65][61][66] It was isolated from thetoadIncilius alvarius (formerlyBufo alvarius and also known as the Sonoran Desert toad, Colorado River toad, or simply bufo) byVittorio Erspamer by 1965.[11][6][67][68]
Alexander Shulgin briefly reported that 5-MeO-DMT was hallucinogenic in humans, viaparenteral but notoralroutes, in 1970, with additional details published later on.[60][65][69][70][71][3]Albert Most, real name Ken Nelson, was the first to describe the use ofIncilius alvarius toadvenom as a psychedelic in his published pamphletBufo Alvarius: the Psychedelic Toad of the Sonoran Desert in 1984.[11] Subsequently,Andrew Weil andWade Davis, in part citing the pamphlet, described the psychoactive effects of the toad in thescientific literature in 1992.[14][72] In addition, they described the finding as the first instance of a psychedelic from an animal source to be discovered.[14]Recreational use of the toads, beyond the pamphlet, was encountered by the late 1980s and became a media sensation.[73] 5-MeO-DMT became acontrolled substance in theUnited States in 2009.[6]
As astructural analog ofN,N-dimethyltryptamine (DMT), 5-MeO-DMT is aSchedule 9 prohibited substance under thePoisons Standard.[74]
5-MeO-DMT is legal for personal use and possession in Canada,[75] though sale, distribution, and other activities involving the substance are illegal under Canadian federal law.
As of October 2015, 5-MeO-DMT is acontrolled substance inChina.[76]
As of 2001 5-MeO-DMT is listed as a controlled substance. Attachement I BtMG. BGBl. I 2001, 1180 - 1186;
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.[77]
5-MeO-DMT has been controlled inTurkey since December 2013.[78]
5-MeO-DMT was made aSchedule Icontrolled substance in January 2011.[79]
A 2019 European study with 42 volunteers showed that a single inhalation of 5-MeO-DMT produced sustained enhancement ofsatisfaction with life, and easing ofanxiety,depression, andpost-traumatic stress disorder (PTSD).[53] A 2018 study found that a single dose of 5-MeO-DMT inducedneurogenesis in mice.[80]
5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients withtreatment-resistant depression (TRD).[81]Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers[82] and phase 1/2 study in TRD patients where 87.5% of patients with TRD were brought into remission on day 7 in the phase 2 part of the study.[83][84] GH Research is currently planning a phase 2b study in TRD patients and have received approval for studies in patients with bipolar II disorder and a current depressive episode and patients with postpartum depression.[85]
In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients withtreatment-resistant depression (TRD).[86] 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.[86] The trial also met allsecondary endpoints, and the treatment was well-tolerated with noserious adverse events reported.[86]
Beckley Psytech in collaboration with King's College London is evaluating the safety and tolerability of intranasal 5-MeO-DMT in healthy subjects, in a phase 1 study.[87][88] Beckley Psytech CEO Cosmo Feilding-Mellen sees a potential in the short-acting nature of 5-MeO-DMT compared to psilocybin: "Requiring one or two therapists to sit in a room with a single patient for the entire duration of an MDMA or psilocybin experience, which is essentially a whole working day, is probably going to be very resource-intensive and expensive. There is already a global shortage of psychotherapists, and this poses a potential bottleneck to patient access in the future."[89]
Ultra-short-acting psychedelics likeDMT 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.[90][91]
Concerns have been raised about the potential use of 5-MeO-DMT in medicine due to the extreme and frequently challenging natures of the experiences.[12]
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 [...]
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.
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".
