View source for 5-MeO-DMT

{{Short description|Psychedelic drug}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 477224937
| drug_name = 
| INN = Mebufotenin
| image = 5-MeO-DMT.svg
| image_class = skin-invert-image
| width = 200px
| image2 = 5-MeO-DMT-3d-sticks.png
| image_class2 = bg-transparent
| width2 = 200px

<!-- Clinical data -->
| pregnancy_AU = 
| pregnancy_US = 
| pregnancy_category = 
| routes_of_administration = [[Inhalational administration|Inhalation]], [[Insufflation (medicine)|insufflation]], [[sublingual administration|sublingual]], [[intramuscular injection|intramuscular]], [[intravenous administration|intravenous]], [[oral administration|oral]] (with an {{Abbrlink|MAOI|monoamine oxidase inhibitor}})<ref name="ReckwegUthaugSzabo2022" /><ref name="ShenJiangWinter2010" /><ref name="TiHKAL" />
| class = [[Binding selectivity|Non-selective]] [[serotonin receptor agonist]]; [[Serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[agonist]]; [[Serotonin 5-HT2A receptor agonist|Serotonin 5-HT<sub>2A</sub> receptor agonist]]; [[Serotonergic psychedelic]]; [[Hallucinogen]]
| ATC_prefix = None
| ATC_suffix = 

<!-- Legal status -->
| legal_AU = S9
| legal_BR = F2
| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-07-25}}</ref>
| legal_CA = 
| legal_UK = Class A
| legal_US = Schedule I
| legal_DE = Anlage I
| legal_status = Illegal in China, Sweden, Turkey

<!-- Pharmacokinetic data -->
| bioavailability = [[Oral administration|Oral]]: inactive (without an {{Abbrlink|MAOI|monoamine oxidase inhibitor}}) or weak<ref name="ReckwegUthaugSzabo2022" /><ref name="ShenJiangWinter2010" />
| protein_bound = 
| metabolism = [[Oxidative deamination]] ({{Abbrlink|MAO|monoamine oxidase}}), ''O''-demethylation ([[CYP2D6]])<ref name="ShenJiangWinter2010" /><ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" />
| metabolites = * [[Bufotenin]]<ref name="ShenJiangWinter2010" /><ref name="DourronNicholsSimonsson2023" />
| onset = * [[Inhalational administration|Inhalation]]: seconds or 3–4{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" />
* [[Intranasal administration|Intranasal]]: 3–4{{nbsp}}min<ref name="ShenJiangWinter2010" />
* [[Intranasal administration|Intranasal]]: 5–7{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" />
* [[Intramuscular injection|Intramuscular]]: 1–6{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" />
| elimination_half-life = * General: Minutes<ref name="DourronNicholsSimonsson2023" /> (12–19{{nbsp}}min in mice, 6–16{{nbsp}}min in rats)<ref name="ShenJiangWinter2010" /><ref name="ErmakovaDunbarRucker2022" />
* [[Sublingual administration|Sublingual]]: 28{{nbsp}}min<ref name="BistueMillónNogueraBruno2025">{{cite journal | vauthors = Bistue Millón MB, Noguera L, Bruno D, Vita L, Zanino M, Kassuha DE, Ortiz JE, Feresin GE, Díaz-Dellavalle P, Orosco L, Garcés MA, Diez P, Albarracín SG, Bruno MA | title = Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study | journal = Neuropsychopharmacology | volume = 50| issue = 11| pages = 1715–1723| date = July 2025 | pmid = 40659913 | doi = 10.1038/s41386-025-02167-3 | pmc = 12436647 | pmc-embargo-date = October 1, 2026 | url = }}</ref>
| duration_of_action = * [[Inhalational administration|Inhalation]]: 10–30{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" />
* [[Intranasal administration|Intranasal]]: 45–70{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" /><ref name="ShenJiangWinter2010" />
* [[Intramuscular injection|Intramuscular]]: ≤60{{nbsp}}min<ref name="ReckwegUthaugSzabo2022" />
| excretion = 

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 1019-45-0
| PubChem = 1832
| IUPHAR_ligand = 145
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1766
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X0MKX3GWU9
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08309
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2086
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 7257
| synonyms = 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

<!-- Chemical data -->
| IUPAC_name = 2-(5-Methoxy-1''H''-indol-3-yl)-''N'',''N''-dimethylethanamine
| C = 13 | H = 18 | N = 2 | O = 1
| SMILES = COc2ccc1[nH]cc(CCN(C)C)c1c2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H18N2O/c1-15(2)7-6-10-9-14-13-5-4-11(16-3)8-12(10)13/h4-5,8-9,14H,6-7H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZSTKHSQDNIGFLM-UHFFFAOYSA-N
}}

'''5-MeO-DMT''', also known as '''5-methoxy-''N'',''N''-dimethyltryptamine''', as well as '''''O''-methylbufotenin''' or '''mebufotenin''', is a [[natural product|naturally occurring]] [[psychedelic drug|psychedelic]] of the [[substituted tryptamine|tryptamine]] family.<ref name="ErmakovaDunbarRucker2022">{{cite journal | vauthors = Ermakova AO, Dunbar F, Rucker J, Johnson MW | title = A narrative synthesis of research with 5-MeO-DMT | journal = J Psychopharmacol | volume = 36 | issue = 3 | pages = 273–294 | date = March 2022 | pmid = 34666554 | doi = 10.1177/02698811211050543 | pmc = 8902691 }}</ref><ref name="ReckwegUthaugSzabo2022">{{cite journal | vauthors = Reckweg JT, Uthaug MV, Szabo A, Davis AK, Lancelotta R, Mason NL, Ramaekers JG | title = The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) | journal = J Neurochem | volume = 162 | issue = 1 | pages = 128–146 | date = July 2022 | pmid = 35149998 | pmc = 9314805 | doi = 10.1111/jnc.15587 }}</ref><ref name="DourronNicholsSimonsson2023">{{cite journal | vauthors = Dourron HM, Nichols CD, Simonsson O, Bradley M, Carhart-Harris R, Hendricks PS | title = 5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk? | journal = Psychopharmacology (Berl) | volume = 242| issue = 7| pages = 1457–1479| date = December 2023 | pmid = 38072874 | doi = 10.1007/s00213-023-06517-1 | url = }}</ref><ref name="ShenJiangWinter2010">{{cite journal | vauthors = Shen HW, Jiang XL, Winter JC, Yu AM | title = Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions | journal = Curr Drug Metab | volume = 11 | issue = 8 | pages = 659–666 | date = October 2010 | pmid = 20942780 | pmc = 3028383 | doi = 10.2174/138920010794233495 }}</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">{{cite journal | vauthors = Araújo AM, Carvalho F, Bastos M, Guedes de Pinho P, Carvalho M | title = The hallucinogenic world of tryptamines: an updated review | journal = Archives of Toxicology | volume = 89 | issue = 8 | pages = 1151–1173 | date = August 2015 | pmid = 25877327 | doi = 10.1007/s00204-015-1513-x | bibcode = 2015ArTox..89.1151A | s2cid = 4825078 }}</ref> Slang terms include ''five-methoxy'', ''the power'', ''bufo'', and ''toad venom''.<ref>{{cite web|url=https://thethirdwave.co/psychedelics/5-meo-dmt/|title=Ultimate Guide to 5-MeO-DMT - Experience, Benefits, & Side Effects|date=29 June 2020}}</ref> The drug has been described as the most powerful psychedelic<ref name="LindenRobin2023">{{cite book | vauthors = Linden J, Robin D | title=Psychedelics as Psychiatric Medications | chapter=Other psychedelics | publisher=Oxford University PressOxford | date=2023 | isbn=978-0-19-286360-7 | doi=10.1093/med/9780192863607.003.0008 | page=95–C8P41 | quote=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 [...]}}</ref><ref name="Delgrasso2024" /> and, by journalist [[Michael Pollan]], as the "Mount Everest of psychedelics".<ref name="Delgrasso2024" /><ref name="Hayes2025">{{cite journal | last=Hayes | first=Caroline | title=A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression? | journal=Psychedelic Medicine | date=14 April 2025 | issn=2831-4425 | doi=10.1089/psymed.2024.0049 | url=https://www.liebertpub.com/doi/10.1089/psymed.2024.0049 | access-date=6 May 2025 | article-number=psymed.2024.0049 | url-access=subscription }}</ref>

[[Adverse effect]]s of 5-MeO-DMT include [[illness|sickness]], [[vomiting]], [[headache]], [[chest pressure]], [[fatigue (medical)|fatigue]], [[anxiety]], [[fear]], [[panic|terror]], [[mental confusion|confusion]], [[paranoia]], [[crying]], loss of [[awareness]] and [[motor control]], and [[psychedelic reactivation|reactivation]]s.<ref name="Hayes2025" /> The drug acts as a [[binding selectivity|non-selective]] [[serotonin receptor agonist]], including of the [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub>]] and [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]s, among others.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = | doi-access = free }}</ref> However, 5-MeO-DMT differs from most other serotonergic psychedelics in having 100- to 1,000-fold higher [[affinity (pharmacology)|affinity]] for the serotonin 5-HT<sub>1A</sub> receptor over the serotonin 5-HT<sub>2A</sub> 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 experience]]s in most people who take it.<ref name="Hayes2025" /> Like DMT, 5-MeO-DMT is only active [[parenteral administration|non-orally]] and has a very rapid [[onset of action]] and short [[duration of action|duration]].<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /> However, 5-MeO-DMT is 4- to 20-fold more [[potency (pharmacology)|potent]] than DMT in humans.<ref name="ShenJiangWinter2010" /><ref name="Hayes2025" />

5-MeO-DMT was first described by 1936, was first [[chemical isolation|isolated]] from [[natural product|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 [[recreational drug|recreationally]] and several deaths have been reported in association with its use.<ref name="ErmakovaDunbarRucker2022" /><ref name="MalacaLoFaroTamborra2020">{{cite journal | vauthors = Malaca S, Lo Faro AF, Tamborra A, Pichini S, Busardò FP, Huestis MA | title = Toxicology and Analysis of Psychoactive Tryptamines | journal = Int J Mol Sci | volume = 21 | issue = 23 | date = December 2020 | page = 9279 | pmid = 33291798 | pmc = 7730282 | doi = 10.3390/ijms21239279 | doi-access = free | url = }}</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">{{cite journal | vauthors = Sexton JD, Nichols CD, Hendricks PS | title = Population Survey Data Informing the Therapeutic Potential of Classic and Novel Phenethylamine, Tryptamine, and Lysergamide Psychedelics | journal = Front Psychiatry | volume = 10 | issue = | article-number = 896 | date = 2019 | pmid = 32116806 | pmc = 7026018 | doi = 10.3389/fpsyt.2019.00896 | doi-access = free | url = }}</ref> 5-MeO-DMT is being developed for potential use in medicine in the treatment of [[neuropsychiatric disorder]]s such as [[depression (mood)|depression]].<ref name="Hayes_2025">{{cite journal | vauthors = Hayes C | title = A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression? | journal = Psychedelic Medicine | date = 14 April 2025 | article-number = psymed.2024.0049 | doi = 10.1089/psymed.2024.0049 | issn = 2831-4425 | url = https://www.liebertpub.com/doi/10.1089/psymed.2024.0049 | access-date = 6 May 2025 | url-access = subscription }}</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 [[oral administration|orally active]], requiring a [[parenteral administration|parenteral]] [[route of administration|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 of action|duration]] than it would have otherwise.<ref name="TiHKAL-Harmaline">{{cite web | title=Erowid Online Books : "TIHKAL" - #13 HARMALINE | website=www.erowid.org | url=http://www.erowid.org/library/books_online/tihkal/tihkal13.shtml | access-date=11 April 2025}}</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>{{cite journal | vauthors = Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR | title = 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety | journal = The American Journal of Drug and Alcohol Abuse | volume = 45 | issue = 2 | pages = 161–169 | date = March 2019 | pmid = 30822141 | pmc = 6430661 | doi = 10.1080/00952990.2018.1545024 }}</ref><ref>{{cite journal | vauthors = Davis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E | title = The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption | journal = Journal of Psychopharmacology | volume = 32 | issue = 7 | pages = 779–792 | date = July 2018 | pmid = 29708042 | pmc = 6248886 | doi = 10.1177/0269881118769063 }}</ref>

===Religious===<!-- [[Church of the Tree of Life]] redirects here -->
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>{{cite book |title=The Book of Sacraments: Ritual Use of Magical Plants | vauthors = Mann J, Gottlieb A |publisher=Ronin Publishing |year=2015 |orig-year=First published 1970|isbn=978-1-57951-210-1|contribution=back cover}}</ref><ref name="Erowid">{{cite web |url=https://www.erowid.org/chemicals/5meo_dmt/5meo_dmt_timeline.php |title=5-MeO-DMT Timeline |work=Erowid}}</ref> Between 1970 and 1990, smoking of 5-MeO-DMT on [[parsley]] was probably one of the two most common forms of [[route of administration|ingestion]] in the [[United States]].<ref name="Erowid"/>{{Unreliable source?|date=October 2023}}

===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 [[Insufflation (medicine)|insufflated]], up to two hours, although the peak effects are usually in the range of 10&ndash;40 minutes.<ref>[https://psychonautwiki.org/wiki/5-MeO-DMT 5-MeO-DMT - PsychonautWiki]</ref> Effects vary and can range from radical perspective shifting and perception of new insights, euphoria, immersive experiences, [[Dissociation (psychology)|dissociation]] and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, panic, and [[ego death]].<ref>{{cite web|url=https://erowid.org/chemicals/5meo_dmt/5meo_dmt_effects.shtml|publisher=Erowid.org|access-date=2021-07-30|title=5-MeO-DMT Effects by Erowid}}</ref>{{Better source needed|reason=Needed reliable source that binds WP:MEDRS |date=May 2023}}

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 [[orgasm]]ic, [[ecstatic]], and [[happiness|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 seizure]]s.<ref name="DourronNicholsSimonsson2023" />

==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Activities of 5-MeO-DMT}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 1.9–28 (K<sub>i</sub>)<br />3.92–1,060 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />68–98% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 14–351 (K<sub>i</sub>)<br />1.53 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />78% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 2.3–20 (K<sub>i</sub>)<br />37 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />98% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 360–528 (K<sub>i</sub>)<br />92–160 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />119% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || 37 (K<sub>i</sub>)<br />14 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />93% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 15–2,011 (K<sub>i</sub>)<br />1.76–784 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />82–106% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 19–3,884 (K<sub>i</sub>)<br />5.9–30 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />21–73% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 42–538 (K<sub>i</sub>)<br />10–31 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />84–90% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || >10,000
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || >10,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || 277–505 (K<sub>i</sub>)<br />110 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />107% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 6.5–78 (K<sub>i</sub>)<br />0.24 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />125% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 3.9–30 (K<sub>i</sub>)<br />65.7 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />107% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[MT1 receptor|MT<sub>1</sub>]] || 210 (K<sub>i</sub>)<br />257 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| [[MT2 receptor|MT<sub>2</sub>]] || 16 (K<sub>i</sub>)<br />112 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| [[Alpha-1A adrenergic receptor|α<sub>1A</sub>]] || 4,373–>10,000
|-
| [[Alpha-1B adrenergic receptor|α<sub>1B</sub>]] || 2,188–>10,000
|-
| [[Alpha-1D adrenergic receptor|α<sub>1D</sub>]] || {{Abbr|ND|No data}}
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 574–1,890
|-
| [[Alpha-2B adrenergic receptor|α<sub>2B</sub>]] || 430–>10,000
|-
| [[Alpha-2C adrenergic receptor|α<sub>2C</sub>]] || 206–2,174
|-
| [[Beta-1 adrenergic receptor|β<sub>1</sub>]] || >10,000
|-
| [[Beta-2 adrenergic receptor|β<sub>2</sub>]] || 2,679–>10,000
|-
| [[Beta-3 adrenergic receptor|β<sub>3</sub>]] || >10,000
|-
| [[D1 receptor|D<sub>1</sub>]] || 80–>10,000
|-
| [[D2 receptor|D<sub>2</sub>]] || 3,562–>10,000
|-
| [[D3 receptor|D<sub>3</sub>]] || 498–>10,000
|-
| [[D4 receptor|D<sub>4</sub>]] || 1,422–>10,000
|-
| [[D5 receptor|D<sub>5</sub>]] || >10,000
|-
| [[H1 receptor|H<sub>1</sub>]] || 7,580–>10,000
|-
| [[H2 receptor|H<sub>2</sub>]]–[[H4 receptor|H<sub>4</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine M1 receptor|M<sub>1</sub>]]–[[Muscarinic acetylcholine M5 receptor|M<sub>5</sub>]] || >10,000
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]] || >10,000
|-
| [[Sigma-2 receptor|σ<sub>2</sub>]] || >10,000
|-
|[[Κ-opioid receptor|KOR]]
|>10,000
|-
| {{Abbrlink|SERT|Serotonin transporter}} || 2,032–>10,000 (K<sub>i</sub>)<br />2,184–>10,000 ([[IC50|{{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})]]<br />>10,000 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || 2,859–>10,000 (K<sub>i</sub>)<br />>10,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />>10,000 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}} || >10,000 (K<sub>i</sub>)<br />>10,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />>10,000 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''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">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 |article-number=e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R | url = }}</ref><ref name="CameronTombariLu2021">{{cite journal | vauthors = Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, Vargas MV, McCarroll MN, Taylor JC, Myers-Turnbull D, Liu T, Yaghoobi B, Laskowski LJ, Anderson EI, Zhang G, Viswanathan J, Brown BM, Tjia M, Dunlap LE, Rabow ZT, Fiehn O, Wulff H, McCorvy JD, Lein PJ, Kokel D, Ron D, Peters J, Zuo Y, Olson DE | title = A non-hallucinogenic psychedelic analogue with therapeutic potential | journal = Nature | volume = 589 | issue = 7842 | pages = 474–479 | date = January 2021 | pmid = 33299186 | pmc = 7874389 | doi = 10.1038/s41586-020-3008-z | bibcode = 2021Natur.589..474C | url = }}</ref><ref name="HalberstadtNicholsGeyer2012">{{cite journal | vauthors = Halberstadt AL, Nichols DE, Geyer MA | title = 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 | journal = Psychopharmacology (Berl) | volume = 221 | issue = 4 | pages = 709–718 | date = June 2012 | pmid = 22222861 | pmc = 3796951 | doi = 10.1007/s00213-011-2616-6 | url = }}</ref><ref name="delaFuenteRevengaFernández-SáezHerrera-Arozamena2015">{{cite journal | vauthors = de la Fuente Revenga M, Fernández-Sáez N, Herrera-Arozamena C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Caignard DH, Rivara S, Rodríguez-Franco MI | title = Novel N-Acetyl Bioisosteres of Melatonin: Melatonergic Receptor Pharmacology, Physicochemical Studies, and Phenotypic Assessment of Their Neurogenic Potential | journal = J Med Chem | volume = 58 | issue = 12 | pages = 4998–5014 | date = June 2015 | pmid = 26023814 | doi = 10.1021/acs.jmedchem.5b00245 | url = }}</ref><wbr /><ref name="BloughLandavazoDecker2014" /><ref name="JayakodiarachchiMaurerSchultz2024" /><ref name="US11440879">{{cite patent | country = US | number = 11440879 | inventor = Andrew Carry Kruegel | status = | title = Methods of treating mood disorders | pubdate = 10 February 2022 | gdate = | fdate = 25 October 2011 | pridate = 25 October 2021 | assign1 = Gilgamesh Pharmaceuticals, Inc. | url = https://patentimages.storage.googleapis.com/c9/f4/7a/7aa95d76398982/US11440879.pdf#page=45}}</ref><ref name="ChenLiYu2023a">{{cite journal | vauthors = Chen X, Li J, Yu L, Maule F, Chang L, Gallant JA, Press DJ, Raithatha SA, Hagel JM, Facchini PJ | title = A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines | journal = J Biol Chem | volume = 299 | issue = 10 | article-number = 105231 | date = October 2023 | pmid = 37690691 | pmc = 10570959 | doi = 10.1016/j.jbc.2023.105231 | doi-access = free | url = }}</ref><ref name="ChenLiYu2023b">{{citation | vauthors = Chen X, Li J, Yu L, Dhananjaya D, Maule F, Cook S, Chang L, Gallant J, Press D, Bains JS, Raithatha S, Hagel J, Facchini P | title=Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery | date=10 March 2023 | doi=10.21203/rs.3.rs-2667175/v1 | doi-access=free | url=https://www.researchsquare.com/article/rs-2667175/latest.pdf | access-date=18 March 2025 | page=}}</ref><ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?testDDRadio=testDDRadio&testLigandDD=1287&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=27 November 2024}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title=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 | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=30707 | access-date=27 November 2024}}</ref><ref name="Puigseslloses_2024" />
|}

5-MeO-DMT is a [[Methoxylation|methoxylated]] [[derivative (chemistry)|derivative]] of [[dimethyltryptamine]] (DMT). While most common psychedelics are believed to primarily elicit psychological effects through [[agonist|agonism]] of [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]s, 5-MeO-DMT shows 1,000-fold greater [[affinity (pharmacology)|affinity]] for the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] over the serotonin 5-HT<sub>2A</sub> receptor.<ref name="Ray2010" /> In line with its affinity for serotonin 5-HT<sub>1A</sub> receptors, 5-MeO-DMT is extremely [[potency (pharmacology)|potent]] at suppressing the firing of [[dorsal raphe nucleus]] serotonin [[neuron]]s.<ref>{{cite journal | vauthors = Rogawski MA, Aghajanian GK | title = Serotonin autoreceptors on dorsal raphe neurons: structure-activity relationships of tryptamine analogs | journal = J Neurosci | volume = 1 | issue = 10 | pages = 1148–1154 | date = October 1981 | doi = 10.1523/JNEUROSCI.01-10-01148.1981 | pmid = 6793698 | pmc = 6564212 }}</ref> Further, its activity in rats was attenuated with the [[binding selectivity|selective]] serotonin 5-HT<sub>1A</sub> receptor [[receptor antagonist|antagonist]] [[WAY-100635]], while selective serotonin 5-HT<sub>2A</sub> receptor antagonist [[volinanserin]] failed to demonstrate any change.<ref>{{cite journal | vauthors = Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA | title = The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats | journal = Psychopharmacology | volume = 189 | issue = 3 | pages = 319–329 | date = December 2006 | pmid = 17013638 | doi = 10.1007/s00213-006-0566-1 | s2cid = 23396616 }}</ref> Additional [[mechanism of action|mechanisms of action]] such as [[reuptake inhibitor|inhibition]] of [[monoamine]] [[reuptake]] may also be involved in its effects.<ref>{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref>

Similarly to other serotonergic psychedelics, 5-MeO-DMT is a [[binding selectivity|non-selective]] [[serotonin receptor agonist]], including of the serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, [[5-HT2B receptor|5-HT<sub>2B</sub>]], and [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]]s, among others.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="JayakodiarachchiMaurerSchultz2024">{{cite journal | vauthors = Jayakodiarachchi N, Maurer MA, Schultz DC, Dodd CJ, Thompson Gray A, Cho HP, Boutaud O, Jones CK, Lindsley CW, Bender AM | title = Evaluation of the Indazole Analogs of 5-MeO-DMT and Related Tryptamines as Serotonin Receptor 2 Agonists | journal = ACS Med Chem Lett | volume = 15 | issue = 2 | pages = 302–309 | date = February 2024 | pmid = 38352850 | pmc = 10860182 | doi = 10.1021/acsmedchemlett.3c00566 | url = }}</ref><ref name="BloughLandavazoDecker2014" /><ref name="Puigseslloses_2024">{{cite journal |vauthors=Puigseslloses P, Nadal-Gratacós N, Ketsela G, Weiss N, Berzosa X, Estrada-Tejedor R, Islam MN, Holy M, Niello M, Pubill D, Camarasa J, Escubedo E, Sitte HH, López-Arnau R |date=August 2024 |title=Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties |journal=Molecular Psychiatry |volume=29 |issue=8 |pages=2346–2358 |doi=10.1038/s41380-024-02506-8 |pmc=11412900 |pmid=38486047}}</ref> It is 4- to 10-fold more [[potency (pharmacology)|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-HT2A receptor|5-HT<sub>2A</sub> receptor]].<ref name="DourronNicholsSimonsson2023" /> In any case, 5-MeO-DMT does still activate the serotonin 5-HT<sub>2A</sub> 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 [[binding selectivity|selectivity]] for the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] over the serotonin 5-HT<sub>2A</sub> receptor and that the actions of 5-MeO-DMT appear to be primarily mediated by serotonin 5-HT<sub>1A</sub> receptor activation.<ref name="ReckwegUthaugSzabo2022" /><ref name="DourronNicholsSimonsson2023" /><ref name="ShenJiangWinter2010" /><ref name="HolzeSinghLiechti2024" /> For example, the [[potency (pharmacology)|potencies]] of drugs substituting for 5-MeO-DMT in [[drug discrimination]] assays is well-correlated with their serotonin 5-HT<sub>1A</sub> receptor [[affinity (pharmacology)|affinities]], and the [[discriminative stimulus]] effects of 5-MeO-DMT are attenuated by serotonin 5-HT<sub>1A</sub> receptor [[receptor antagonist|antagonist]]s.<ref name="ShenJiangWinter2010" /> However, there is partial [[stimulus generalization|generalization]] of 5-MeO-DMT to the selective serotonin [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] agonist [[DOM (drug)|(–)-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<sub>1A</sub> receptor than for the serotonin 5-HT<sub>2A</sub> receptor, the situation appears to be very different in terms of its actual activational potencies at these receptors.<ref name="CummingScheideggerDornbierer2021">{{cite journal | vauthors = Cumming P, Scheidegger M, Dornbierer D, Palner M, Quednow BB, Martin-Soelch C | title = Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans | journal = Molecules | volume = 26 | issue = 9 | date = April 2021 | page = 2451 | pmid = 33922330 | pmc = 8122807 | doi = 10.3390/molecules26092451 | doi-access = free | url = }}</ref><ref name="BloughLandavazoDecker2014" /><ref name="CameronTombariLu2021" /> Its {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} values have been found to be 1.80 to 3.87{{nbsp}}nM at the serotonin 5-HT<sub>2A</sub> receptor and 3.92 to 1,060{{nbsp}}nM at the serotonin 5-HT<sub>1A</sub> receptor.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" /><ref name="CameronTombariLu2021" /><ref name="BindingDB" /> For comparison, the {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} values of DMT were found to be 38.3{{nbsp}}nM at the serotonin 5-HT<sub>2A</sub> receptor and >10,000{{nbsp}}nM at the serotonin 5-HT<sub>1A</sub> 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<sub>2A</sub> receptor than of the serotonin 5-HT<sub>1A</sub> 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<sub>2A</sub> receptor.<ref name="CummingScheideggerDornbierer2021" /><ref name="BloughLandavazoDecker2014" />

Besides the serotonin receptors, 5-MeO-DMT is an [[agonist]] of the [[melatonin receptor|melatonin]] [[MT1 receptor|MT<sub>1</sub>]] and [[MT2 receptor|MT<sub>2</sub> receptor]]s.<ref name="delaFuenteRevengaFernández-SáezHerrera-Arozamena2015" /><ref name="BindingDB" /><ref name="PDSPKiDatabase" /> Unlike DMT, 5-MeO-DMT is not a [[ligand (biochemistry)|ligand]] or agonist of the [[sigma receptor]]s.<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 {{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} value of 2,184{{nbsp}}nM.<ref name="BloughLandavazoDecker2014" /> Conversely, it is inactive as a [[dopamine reuptake inhibitor|dopamine]] and [[norepinephrine reuptake inhibitor]] ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} = >10,000{{nbsp}}nM).<ref name="BloughLandavazoDecker2014" />

Similarly to DMT, but in contrast to most other psychedelics, like LSD and psilocybin,<ref name="Halberstadt2015">{{cite journal | vauthors = Halberstadt AL | title = Recent advances in the neuropsychopharmacology of serotonergic hallucinogens | journal = Behav Brain Res | volume = 277 | issue = | pages = 99–120 | date = January 2015 | pmid = 25036425 | doi = 10.1016/j.bbr.2014.07.016 | pmc = 4642895 | url = }}</ref><ref name="JiménezBouso2022">{{cite journal | vauthors = Jiménez JH, Bouso JC | title = Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate | journal = J Psychopharmacol | volume = 36 | issue = 8 | pages = 905–919 | date = August 2022 | pmid = 35695604 | doi = 10.1177/02698811221104054 | url = }}</ref> there appears to be very little development of [[drug tolerance|tolerance]] with 5-MeO-DMT.<ref name="ErmakovaDunbarRucker2022" /><ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology (Berl) | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 | url = }}</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<sub>2A</sub> receptor.<ref name="ErmakovaDunbarRucker2022" /> More specifically, 5-MeO-DMT activates the [[Gq protein|G<sub>q</sub>]] [[cell signaling|signaling pathway]] of the serotonin 5-HT<sub>2A</sub> receptor with much less [[potency (pharmacology)|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">{{cite journal | vauthors = Barksdale BR, Doss MK, Fonzo GA, Nemeroff CB | title = The mechanistic divide in psychedelic neuroscience: An unbridgeable gap? | journal = Neurotherapeutics | volume = 21 | issue = 2 | article-number = e00322 | date = March 2024 | pmid = 38278658 | doi = 10.1016/j.neurot.2024.e00322 | pmc = 10963929 | url = }}</ref><ref name="WallachCaoCalkins2023">{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nat Commun | volume = 14 | issue = 1 | article-number = 8221 | date = December 2023 | pmid = 38102107 | doi = 10.1038/s41467-023-44016-1 | pmc = 10724237 | bibcode = 2023NatCo..14.8221W | url = }}</ref>

===Pharmacokinetics===
====Absorption====
5-MeO-DMT is not [[oral administration|orally active]] and must be administered [[parenteral administration|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 [[peripherally selective drug|peripheral selectivity]].<ref name="ShenJiangWinter2010" /><ref name="PlazasFaraone2023">{{cite journal | vauthors = Plazas E, Faraone N | title = Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents | journal = Biomedicines | volume = 11 | issue = 2 | date = February 2023 | page = 461 | pmid = 36830997 | pmc = 9953455 | doi = 10.3390/biomedicines11020461 | doi-access = free | url = }}</ref><ref name="McBride2000">{{cite journal | vauthors = McBride MC | title = Bufotenine: toward an understanding of possible psychoactive mechanisms | journal = J Psychoactive Drugs | volume = 32 | issue = 3 | pages = 321–331 | date = 2000 | pmid = 11061684 | doi = 10.1080/02791072.2000.10400456 | url = }}</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 (pharmacology)|affinity]] for the serotonin 5-HT<sub>2A</sub> 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 [[drug metabolism|metabolism]] of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by [[monoamine oxidase inhibitor]]s (MAOIs).<ref name="ShenJiangWinter2010" /> In addition, MAOIs allow 5-MeO-DMT to become [[oral administration|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 [[sublingual administration|sublingually]], was found to be 28{{nbsp}}minutes.<ref name="BistueMillónNogueraBruno2025" />

==Chemistry==
5-MeO-DMT, also known as 5-methoxy-''N'',''N''-dimethyltryptamine, is a [[substituted tryptamine]] [[chemical derivative|derivative]]. <ref name="TiHKAL" />It is the 5-[[methoxy group|methoxylated]] derivative of [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT), the ''N'',''N''-[[methyl group|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 [[partition coefficient|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">{{cite journal | vauthors = Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, Lenoch K | title = Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use | journal = ACS Omega | volume = 5 | issue = 49 | pages = 32067–32075 | date = December 2020 | pmid = 33344861 | pmc = 7745443 | doi = 10.1021/acsomega.0c05099 }}</ref><ref>{{cite web | vauthors = Carpenter DE |date=2021-02-02 |title=Psychedelic Toads Pushed To The Limit, Conservationists Urge Synthetic 5-MeO-DMT Option |url=https://www.forbes.com/sites/davidcarpenter/2021/02/02/psychedelic-toads-pushed-to-the-limit-conservationists-urge-synthetic-5-meo-dmt-option/ |access-date=2021-02-04 |website=Forbes |language=en}}</ref>

===Analogues and derivatives===
[[Structural analog|Analogue]]s 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===
{| class="wikitable sortable"
|+ Plant sources
|-
! Family !! Plants 
|-
| [[Rutaceae]] || ''[[Dictyoloma incanescens]]'',<ref>{{cite journal | vauthors = Uthaug MV, Lancelotta R, Szabo A, Davis AK, Riba J, Ramaekers JG | title = Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment | journal = Psychopharmacology | volume = 237 | issue = 3 | pages = 773–785 | date = March 2020 | pmid = 31822925 | pmc = 7036074 | doi = 10.1007/s00213-019-05414-w }}</ref> ''[[Limonia acidissima]]'',<ref name="bluezoo_tryptamines">{{cite web |url=http://bluezoo.org/tryptamines/plants.html|title=tryptamines: fungi |website=bluezoo.org}}</ref> ''[[Melicope leptococca]]''<ref name="erowid_tryptamines">{{cite web |url=https://www.erowid.org/psychoactives/faqs/faqs_tryptamine.shtml |title=Erowid Psychoactive Vaults: Tryptamine FAQ |website=www.erowid.org}}</ref><!-- is melicope from rutaceae or rubiaceae? -->
|-6
| [[Fabaceae]] || ''[[Anadenanthera peregrina]]'',<ref name="trout_notes">{{cite web |url=https://troutsnotes.com/pdf/SomeSimpleTryptamines_2ndEd_2007_with_addendum.pdf |title= Some simple tryptomines |website=troutsnotes.com |access-date=2020-07-04}}</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"/> ''[[Virola calophylla|V. calophylla]]'',<ref name="forensic_chemistry" /> ''[[Virola multinervia|V. multinervia]]'',<ref name="forensic_chemistry" /> ''[[Virola peruviana|V. peruviana]]'',<ref name="forensic_chemistry" /> ''[[Virola rufula|V. rufula]]'',<ref name="forensic_chemistry" /> ''[[Virola venosa|V. venosa]]''<ref name="forensic_chemistry" />
|}

===Toads===
[[File:Bufo alvarius1.jpg|thumb|Colorado River toad]]

{| class="wikitable sortable"
|+ Animal Sources
|-
! Family !! Animals 
|-
| [[Bufonidae]] || [[Colorado River toad]] (''Incilius alvarius'')<ref>{{cite web |url=https://www.forbes.com/sites/davidcarpenter/2020/02/02/5-meo-dmt-the-20-minute-psychoactive-toad-experience-thats-transforming-lives/ |title=5-MeO-DMT: The 20-Minute Psychoactive Toad Experience That's Transforming Lives | vauthors = Carpenter DE |website=Forbes}}</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 gland|parotoid]] secretions of the animal produces a powerful and short-lived [[psychedelic experience]].<ref>{{cite web | vauthors = Nelson K |others= Illustrated by Gail Patterson |title=Bufo alvarius: The Psychedelic Toad of the Sonoran Desert |url=https://www.erowid.org/archive/sonoran_desert_toad/almost.htm |access-date=October 20, 2023 |website=[[Erowid]]}}</ref> The smoking of ''I. alvarius'' secretions should not be confused with the urban legend of [[toad licking]].<ref name="TiHKAL">{{cite web | vauthors = Shulgin A, Shulgin A |title=Tryptamines I Have Known And Loved: The Continuation |date=1997|url=https://erowid.org/library/books_online/tihkal/tihkal38.shtml |access-date=October 20, 2023 |website=[[Erowid]]}}</ref> Since 1983, the animal has become a popular source of 5-MeO-DMT for recreational or [[Entheogen|spiritual purposes]].<ref>{{cite news | vauthors = Romero S |date=2022-03-20 |title=Demand for This Toad's Psychedelic Toxin Is Booming. Some Warn That's Bad for the Toad. |language=en-US |work=The New York Times |url=https://www.nytimes.com/2022/03/20/us/toad-venom-psychedelic.html |access-date=2023-10-20 |issn=0362-4331}}</ref> Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.<ref>{{cite web |date=2023-07-12 |title=The Sonoran Desert toad can get you high. Poachers have taken notice. |url=https://www.nationalgeographic.com/animals/article/sonoran-desert-toad-dmt-psychedelic-movement |archive-url=https://web.archive.org/web/20230712175204/https://www.nationalgeographic.com/animals/article/sonoran-desert-toad-dmt-psychedelic-movement |url-status=dead |archive-date=July 12, 2023 |access-date=2023-10-20 |website=Animals |language=en}}</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>{{cite book | vauthors = Morris H |date=2021-02-02 | chapter = Preface | edition = 2021 | title = Bufo alvarius: The Psychedelic Toad of the Sonoran Desert | chapter-url= https://www.psychedelictoadofthesonorandesert.com/preface |url-status=live |archive-url= https://web.archive.org/web/20210202114012/https://www.psychedelictoadofthesonorandesert.com/preface|archive-date= 2021-02-02|access-date=2023-10-20 }}</ref>

===Fungi===
{| class="wikitable sortable"
|+ Fungal Sources
|-
! Family !! Fungi
|-
| [[Amanitaceae]] || ''[[Amanita citrina]]'',<ref name="forensic_chemistry">{{cite book | vauthors = Khan JI, Kennedy TJ, Christian JR DR |title= Basic Principles of Forensic Chemistry |date=2011 |publisher=Springer Science & Business Media |isbn=978-1-934115-06-0 |pages=195 |url=https://books.google.com/books?id=9qrXBjRF388C&pg=PA195 }}</ref> ''[[Amanita porphyria]]''<ref name="forensic_chemistry" />
|}

==History==
5-MeO-DMT was first [[chemical synthesis|synthesized]] by [[:ja:星野敏雄|Toshio Hoshino]] in 1935.<ref name="Delgrasso2024">{{cite journal | vauthors = Delgrasso A | title=Defining 5-MeO-DMT in Historical and Cultural Contexts | journal=World Futures | volume=80 | issue=2 | date=17 February 2024 | issn=0260-4027 | doi=10.1080/02604027.2024.2330255 | pages=174–197 | url=https://www.researchgate.net/publication/379130421 | quote=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.}}</ref><ref name="ErmakovaDunbarRucker2022" /><ref name="HoshinoShimodaira1936">{{cite journal | vauthors = Hoshino T, Shimodaira K | title=Über die synthese des bufotenin-methyl-äthers (5-methoxy-n-dimethyl-tryptamin) und bufotenins (synthesen in der indol-gruppe. XV) | journal=Bulletin of the Chemical Society of Japan | volume=11 | issue=3 | date=1 March 1936 | issn=0009-2673 | doi=10.1246/bcsj.11.221 | doi-access=free | pages=221–224 }}</ref> It was [[chemical isolation|isolated]] from the [[flowering plant]] ''[[Dictyoloma incanescens]]'' in 1959.<ref name="ErmakovaDunbarRucker2022" /><ref name="PachterZachariasRibeiro1959">{{cite journal | vauthors = Pachter IJ, Zacharias DE, Ribeiro O | title=Indole Alkaloids of Acer saccharinum (the Silver Maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis | journal=The Journal of Organic Chemistry | volume=24 | issue=9 | date=1959 | issn=0022-3263 | doi=10.1021/jo01091a032 | pages=1285–1287}}</ref> The drug was subsequently isolated from numerous other [[plant]], [[fungi|fungal]], and [[animal]] [[natural product|source]]s 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">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1}}</ref><ref name="GessnerGodseKrull1968">{{cite journal | vauthors = Gessner PK, Godse DD, Krull AH, McMullan JM | title = Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines | journal = Life Sci | volume = 7 | issue = 5 | pages = 267–277 | date = March 1968 | pmid = 5641719 | doi = 10.1016/0024-3205(68)90200-2 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=b45d79b71663e4451de894d16a1c868141dfeaaf| url-access = subscription }}</ref><ref name="GessnerMcIsaacPage1961">{{cite journal | vauthors = GESSNER PK, McISAAC WM, PAGE IH | title = Pharmacological actions of some methoxyindolealkylamines | journal = Nature | volume = 190 | issue = 4771| pages = 179–180 | date = April 1961 | pmid = 13704827 | doi = 10.1038/190179a0 | bibcode = 1961Natur.190..179G | url = }}</ref><ref name="GessnerIrvine1962">{{cite journal | vauthors = Gessner PK, Page IH | title=Behavioral effects of 5-methoxy-N:N-dimethyltryptamine, other tryptamines, and LSD | journal=American Journal of Physiology. Legacy Content | volume=203 | issue=1 | date=1 July 1962 | issn=0002-9513 | doi=10.1152/ajplegacy.1962.203.1.167 | pages=167–172}}</ref><ref name="GallagherKochMoore1964">{{cite journal | vauthors = Gallagher CH, Koch JH, Moore RM, Steel JD | title = Toxicity of Phalaris tuberosa for Sheep | journal = Nature | volume = 204 | issue = 4958| pages = 542–545 | date = November 1964 | pmid = 14238156 | doi = 10.1038/204542a0 | bibcode = 1964Natur.204..542G | url = }}</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">{{cite journal | vauthors = Holmstedt B | title = Tryptamine derivatives in Epená, an intoxicating snuff used by some South American Indian tribes | journal = Arch Int Pharmacodyn Ther | volume = 156 | issue = 2 | pages = 285–305 | date = August 1965 | pmid = 5868939 | doi = | url = }}</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">{{cite journal | vauthors = Erspamer V, Vitali T, Roseghini M, Cei JM | title = 5-Methoxy- and 5-hydroxy-indolealkylamines in the skin of Bufo alvarius | journal = Experientia | volume = 21 | issue = 9 | pages = 504 | date = September 1965 | pmid = 5872604 | doi = 10.1007/BF02138956 | url = https://link.springer.com/content/pdf/10.1007/BF02138956.pdf}}</ref><ref name="EspamerVitaliRoseghini1967">{{cite journal | vauthors = Erspamer V, Vitali T, Roseghini M, Cei JM | title = 5-Methoxy- and 5-hydroxyindoles in the skin of Bufo alvarius | journal = Biochem Pharmacol | volume = 16 | issue = 7 | pages = 1149–1164 | date = July 1967 | pmid = 6053590 | doi = 10.1016/0006-2952(67)90147-5 | url = https://core.ac.uk/download/pdf/286811965.pdf}}</ref>

[[Alexander Shulgin]] briefly reported that 5-MeO-DMT was hallucinogenic in humans, via [[parenteral administration|parenteral]] but not [[oral administration|oral]] [[route of administration|route]]s, in 1970, with additional details published later on.<ref name="BrimblecombePinder1975" /><ref name="Shulgin1976">{{cite book | veditors=Gordon M | title=Psychopharmacological Agents: Use, Misuse and Abuse | series=Medicinal Chemistry: A Series of Monographs | volume=4 | vauthors = Shulgin AT | chapter=Psychotomimetic Agents | date=1976 | isbn=978-0-12-290559-9 | doi=10.1016/b978-0-12-290559-9.50011-9 | pages=59–146 | publisher=Academic Press | chapter-url=https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9}}</ref><ref name="Shulgin1970">{{cite book | author = [[Alexander Shulgin]] | chapter = Chemistry and Structure-Activity Relationships of the Psychotomimetics | editor = D. H. Efron | title = Psychotomimetic Drugs | publisher = Raven Press | location = New York | pages = 21–41 | date = 1970 | url = https://www.erowid.org/library/books_online/psychotomimetic_drugs.pdf#page=23 }}</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">{{cite journal | vauthors = de Smet PA | title = A multidisciplinary overview of intoxicating enema rituals in the western hemisphere | journal = J Ethnopharmacol | volume = 9 | issue = 2–3 | pages = 129–166 | date = December 1983 | pmid = 6677814 | doi = 10.1016/0378-8741(83)90031-4 | url = | quote = 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".}}</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 (anthropologist)|Wade Davis]], in part citing the pamphlet, described the psychoactive effects of the toad in the [[scientific literature]] in 1992.<ref name="WeilDavis1994">{{cite journal | vauthors = Weil AT, Davis W | title = Bufo alvarius: a potent hallucinogen of animal origin | journal = J Ethnopharmacol | volume = 41 | issue = 1–2 | pages = 1–8 | date = January 1994 | pmid = 8170151 | doi = 10.1016/0378-8741(94)90051-5 | url = https://www.reptilis.org/pdf/Amphibiens/Bufo%20alvarius-%20a%20potent%20hallucinogen%20of%20animal%20origin.pdf}}</ref><ref name="DavisWeil1992">{{cite journal | vauthors = Davis W, Weil AT | title=Identity of a New World Psychoactive Toad | journal=Ancient Mesoamerica | volume=3 | issue=1 | date=1992 | issn=0956-5361 | doi=10.1017/S0956536100002297 | pages=51–59}}</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 drug|Recreational use]] of the toads, beyond the pamphlet, was encountered by the late 1980s and became a media sensation.<ref name="Lyttle1993">{{cite journal | vauthors = Lyttle T | title = Misuse and legend in the "toad licking" phenomenon | journal = Int J Addict | volume = 28 | issue = 6 | pages = 521–538 | date = May 1993 | pmid = 8486435 | doi = 10.3109/10826089309039645 | url = }}</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 term|generic name]] of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}. 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 [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 9: prohibited substance|Schedule 9]] prohibited substance under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard]].<ref>{{cite web |title=Poisons Standard July 2016 |date=24 June 2016 |url=https://www.legislation.gov.au/Details/F2016L01071 |publisher=Federal Register of Legislation}}</ref>

====Canada====
5-MeO-DMT is legal for personal use and possession in Canada,<ref>{{cite web |title=Is 5-MeO-DMT (Bufo) Legal in Canada? Understanding 5-MeO-DMT Laws and Regulations |url=https://www.psychedeliclaw.ca/5meodmt-bufotenin |access-date=2023-11-28 |website=PsychedelicLaw.ca |language=en-US}}</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>{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=Chinese | access-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | archive-date=1 October 2015 | url-status=dead }}</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>{{cite web | url=https://www.notisum.se/rnp/sls/sfs/20040696.pdf | title=Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor | work=Svensk författningssamling | date=7 September 2004 | language=sv}}</ref>

====Turkey====
5-MeO-DMT has been controlled in [[Turkey]] since December 2013.<ref>{{cite web | url=http://www.resmigazete.gov.tr/eskiler/2014/01/20140125-3-1.pdf | title=Turkish Law | work=Resmi Gazete | date=16 December 2013}}</ref>

====United States====
5-MeO-DMT was made a [[List of Schedule I drugs (US)|Schedule I]] [[Controlled Substances Act|controlled substance]] in January 2011.<ref>{{cite journal | author = Drug Enforcement Administration (DEA), Department of Justice | title = Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule | journal = Federal Register | volume = 75 | issue = 243 | pages = 79296–79300 | date = December 2010 | pmid = 21171485 | url = https://www.gpo.gov/fdsys/pkg/FR-2010-12-20/pdf/2010-31854.pdf }}</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]], [[Mood disorder#Depressive disorders|depression]], and [[post-traumatic stress disorder]] (PTSD).<ref name=pmid30982127>{{cite journal | vauthors = Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KP, Mason N, Rak J, Šuláková A, Jurok R, Maryška M, Kuchař M, Páleníček T, Riba J, Ramaekers JG | title = 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 | journal = Psychopharmacology | volume = 236 | issue = 9 | pages = 2653–2666 | date = September 2019 | pmid = 30982127 | pmc = 6695371 | doi = 10.1007/s00213-019-05236-w | doi-access = free }}</ref> A 2018 study found that a single dose of 5-MeO-DMT induced [[neurogenesis]] in mice.<ref>{{cite journal | vauthors = Lima da Cruz RV, Moulin TC, Petiz LL, Leão RN | title = A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus | journal = Frontiers in Molecular Neuroscience | volume = 11 | article-number = 312 | date = 2018 | pmid = 30233313 | pmc = 6131656 | doi = 10.3389/fnmol.2018.00312 | doi-access = free }}</ref>

===Depression===
{{See also|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).<ref>{{cite web|url=https://www.ghres.com/|title=Home &#124; GH Research|website=GH Research Limited}}</ref> [[Biopharmaceutical]] company GH Research has sponsored a completed phase 1 study in healthy volunteers<ref>{{cite journal | vauthors = Reckweg J, Mason NL, van Leeuwen C, Toennes SW, Terwey TH, Ramaekers JG | title = 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 | journal = Frontiers in Pharmacology | volume = 12 | article-number = 760671 | date = 2021 | pmid = 34912222 | pmc = 8667866 | doi = 10.3389/fphar.2021.760671 | doi-access = free }}</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">{{cite journal | vauthors = Reckweg JT, van Leeuwen CJ, Henquet C, van Amelsvoort T, Theunissen EL, Mason NL, Paci R, Terwey TH, Ramaekers JG | title = 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 | journal = Front Psychiatry | volume = 14 | issue = | article-number = 1133414 | date = 2023 | pmid = 37409159 | pmc = 10319409 | doi = 10.3389/fpsyt.2023.1133414 | doi-access = free | url = }}</ref><ref>{{cite press release | author = GH Research PLC |date=2021-12-06 |title=GH Research Announces Successful Outcome of the Phase 2 part of its Phase 1/2 Clinical Trial of GH001 in Treatment-Resistant Depression |url=https://www.globenewswire.com/en/news-release/2021/12/06/2346425/0/en/GH-Research-Announces-Successful-Outcome-of-the-Phase-2-part-of-its-Phase-1-2-Clinical-Trial-of-GH001-in-Treatment-Resistant-Depression.html |access-date=2022-10-07 |website=GlobeNewswire News Room |language=en}}</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>{{cite press release | author =GH Research PLC|date=2022-08-23 |title=GH Research Reports Second Quarter 2022 Financial Results and Provides Business Updates |url=https://www.globenewswire.com/en/news-release/2022/08/23/2502831/0/en/GH-Research-Reports-Second-Quarter-2022-Financial-Results-and-Provides-Business-Updates.html |access-date=2022-10-07 |website=GlobeNewswire News Room |language=en}}</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|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|Montgomery-Åsberg Depression Rating Scale (MADRS)]] at day 8, with 57.7% of patients achieving [[Remission (medicine)|remission]] compared to 0% in the placebo group.<ref name="GHResearch2025" /> The trial also met all [[secondary endpoint]]s, and the treatment was well-tolerated with no [[serious adverse event]]s reported.<ref name="GHResearch2025">{{Cite news | vauthors = Ryan J |date=February 3, 2025 |title=GH Research Announces Primary Endpoint Met in Phase 2b Trial with GH001 in TRD Demonstrating -15.5 Point Placebo-adjusted MADRS Reduction |url=https://investor.ghres.com/news-releases/news-release-details/gh-research-announces-primary-endpoint-met-phase-2b-trial-gh001 |access-date=February 16, 2025}}</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>{{cite web | vauthors = Carpenter DE |date=2022-02-16 |title=More Companies Embrace 5-MeO-DMT to Create Therapies |url=https://www.lucid.news/companies-embrace-5-meo-dmt-therapies/ |access-date=2022-03-06 |website=Lucid News |language=en-US}}</ref><ref>{{Cite press release |author = Atai Life Sciences |date=2024-03-27 |title=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 |url=https://www.globenewswire.com/news-release/2024/03/27/2853041/0/en/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.html |access-date=2024-10-06 |website=GlobeNewswire News Room |language=en}}</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>{{cite news | vauthors = Siebert A |title=Could 5-MeO-DMT Allow For More Affordable Psychedelic-Assisted Therapy? Beckley Psytech Thinks So |url=https://www.forbes.com/sites/amandasiebert/2022/02/28/could-5-meo-dmt-allow-for-more-affordable-psychedelic-assisted-therapy--beckley-psytech-thinks-so/ |access-date=2022-03-06 |website=Forbes |language=en}}</ref>

Ultra-short-acting psychedelics like [[dimethyltryptamine|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">{{cite journal | vauthors = Ramaekers JG | title = Less is more? Antidepressant effects of short-acting psychedelics | journal = Neuropsychopharmacology | volume = 50 | issue = 6 | pages = 875–876 | date = May 2025 | pmid = 40258989 | pmc = 12032289 | doi = 10.1038/s41386-025-02103-5 | pmc-embargo-date = May 1, 2026 }}</ref><ref name="RamaekersReckwegMason2025">{{cite journal | vauthors = Ramaekers JG, Reckweg JT, Mason NL | title = Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression | journal = The American Journal of Psychiatry | volume = 182 | issue = 1 | pages = 33–46 | date = January 2025 | pmid = 39741439 | doi = 10.1176/appi.ajp.20230890 | url = https://cris.maastrichtuniversity.nl/en/publications/fb3d3cba-472c-42bf-b665-bf9607461199 }}</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]]

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/5038 5-MeO-DMT - Isomer Design]
* [https://psychonautwiki.org/wiki/5-MeO-DMT 5-MeO-DMT - PsychonautWiki]
* [https://www.erowid.org/chemicals/5meo_dmt/5meo_dmt.shtml 5-MeO-DMT - Erowid]
* [https://www.erowid.org/library/books_online/tihkal/tihkal38.shtml 5-MeO-DMT - TiHKAL - Erowid]
* [https://isomerdesign.com/PiHKAL/read.php?domain=tk&id=38 5-MeO-DMT - TiHKAL - Isomer Design]
* [https://tripsitter.com/5-meo-dmt/ 5-MeO-DMT: Unpacking The Mysteries of This Powerful Psychedelic - Tripsitter]

{{Psychedelics}}
{{Serotonin receptor modulators}}
{{Melatonin receptor modulators}}
{{Tryptamines}}

{{DEFAULTSORT:MeO-DMT, 5-}}

[[Category:5-HT1A agonists]]
[[Category:5-HT1B agonists]]
[[Category:5-HT1D agonists]]
[[Category:5-HT1E agonists]]
[[Category:5-HT1F agonists]]
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[[Category:5-HT2B agonists]]
[[Category:5-HT2C agonists]]
[[Category:5-HT5A agonists]]
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[[Category:Ayahuasca]]
[[Category:Biased ligands]]
[[Category:Designer drugs]]
[[Category:N,N-Dialkyltryptamines]]
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[[Category:Entheogens]]
[[Category:Experimental hallucinogens]]
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[[Category:5-Methoxytryptamines]]
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