5-MeO-DMT

5-methoxy-N,N-dimethyltryptamine

6Node page

what any key link opens

psx:substance/5-meo-dmt/section/clinical-evidence.full@1

sectionreferenced by edges — no row of its own

derived from · upstream

informed_byClaim in clinical-evidence — supportedpsx:substance/5-meo-dmt/claim/ae76ff58-64b6-4241-8a42-6beb0e3ca5a8
informed_byClaim in clinical-evidence — supportedpsx:substance/5-meo-dmt/claim/4443f80a-ba76-458d-9278-f50a05e2d797
informed_byClaim in clinical-evidence — supportedpsx:substance/5-meo-dmt/claim/82dec6c1-3c09-46ff-868d-578ab1a93eee
informed_byClaim in clinical-evidence — supportedpsx:substance/5-meo-dmt/claim/747b872f-aec8-484b-8c24-dc46a39d6487

feeds · downstream

none recorded

psx:substance/5-meo-dmt/section/clinical-evidence.full@1
├─ informed_by  claim/ae76ff58-64b6-4241-8a42-6beb0e3ca5a8  Claim in clinical-evidence — supported
├─ informed_by  claim/4443f80a-ba76-458d-9278-f50a05e2d797  Claim in clinical-evidence — supported
├─ informed_by  claim/82dec6c1-3c09-46ff-868d-578ab1a93eee  Claim in clinical-evidence — supported
├─ informed_by  claim/747b872f-aec8-484b-8c24-dc46a39d6487  Claim in clinical-evidence — supported
  ├─ used  src/doi:10.3389/fpsyt.2023.1133414  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
  ├─ used  src/doi:10.1177/02698811241246857  Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants
  ├─ used  src/doi:10.3389/fpsyt.2023.1271152  5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study
  ├─ used  src/doi:10.1007/s00213-019-05414-w  Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment
      ├─ used  src/doi:10.1177/02698811211050543  A narrative synthesis of research with 5-MeO-DMT
      ├─ used  src/doi:10.1111/jnc.15587  The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
      ├─ used  src/url:414e2dfdcbd7f4bd  5-MeO-DMT synthesis history and physical properties
      ├─ used  src/url:2a8b4b20aa361b94  GH Research Phase 2b Trial Results: GH001 in Treatment-Resistant Depression
      ├─ used  src/doi:10.1021/acschemneuro.4c00513  Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-N,N-dimethyltryptamine Analogs in Mice
      ├─ used  src/doi:10.1038/s41380-024-02506-8  Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties
      ├─ used  src/pmid:20942780  Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions
      ├─ used  src/doi:10.3389/fpsyg.2018.02459  Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study
      ├─ used  src/url:fe9db4ee5125b139  Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effects
      ├─ used  src/doi:10.1124/dmd.111.039107  Nonlinear pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine in mice
      ├─ used  src/doi:10.1016/j.bcp.2010.02.020  Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics
      ├─ used  src/doi:10.1124/dmd.112.050724  Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status
      ├─ used  src/doi:10.1021/acschemneuro.2c00170  Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice
      ├─ used  src/pmid:8170151  Bufo alvarius: a potent hallucinogen of animal origin
      ├─ used  src/pmid:12777961  Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase
      ├─ used  src/url:b6a62df3f5c55d24  Legal status of 5-MeO-DMT by jurisdiction
      ├─ used  src/pmid:21171485  Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule.
      ├─ used  src/url:f0ea686fb8fce3db  Usona Institute NCT05698095: IM 5-MeO-DMT Phase 1 PK Study
      ├─ used  src/doi:10.1021/acsomega.0c05099  Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use
      ├─ used  src/doi:10.34133/research.0987  Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and Anxiety
      ├─ used  src/doi:10.1016/j.chemphyslip.2023.105279  Interaction of psychedelic tryptamine derivatives with a lipid bilayer
      ├─ used  src/doi:10.1002/cpt.3459  Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy
      ├─ used  src/pmid:25446678  Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors
      ├─ used  src/url:7f34d9a22c0f2896  IUPHAR/BPS Guide to Pharmacology — 5-MeO-DMT Ligand Activity
      ├─ used  src/doi:10.1208/s12248-008-9028-5  Indolealkylamines: biotransformations and potential drug-drug interactions
      ├─ used  src/doi:10.1007/s40263-025-01250-z  Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept Trial
      ├─ used  src/doi:10.1007/s00213-019-05236-w  A single inhalation of vapor from dried toad secretion containing 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
      ├─ used  src/doi:10.1177/0269881118769063  The epidemiology of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption
      ├─ used  src/doi:10.1016/j.bpsc.2024.01.007  Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile
      ├─ used  src/doi:10.1176/appi.ajp.20230890  Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression
      ├─ used  src/doi:10.1371/journal.pone.0009019  Psychedelics and the human receptorome
      ├─ used  src/doi:10.1126/science.adf0435  Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors
      ├─ used  src/doi:10.2174/1570159X13666141210222409
      ├─ used  src/pmid:7922531  The excitability and rhythm of medullary respiratory neurons in the cat are altered by the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine
      ├─ used  src/doi:10.1177/02698811231211219  Drug-drug interactions involving classic psychedelics: A systematic review
      ├─ derived_from  gen/f9b88989-26da-44e9-988d-310a137d0982  Generation — pipeline-v5
      └─ generated_by  pub/93159458-c861-4065-b1d0-4508b7fc3c2d  Publication — backfill
    ├─ used  version/1  Revision 1
    ├─ used  claim/b9ff2dcc-3a11-45d8-b728-da4172084902  Claim in history — inconclusive  working
    ├─ used  claim/b2b9d27a-d514-4b46-bf18-6992fc1cc08e  Claim in safety — inconclusive  working
    ├─ used  claim/15af084f-6ace-478c-a1a3-6833495bef87  Claim in safety — inconclusive  working
    ├─ used  claim/1d4b003a-7052-470f-948b-db72cfdfcb5e  Claim in safety — inconclusive  working
      ├─ derived_from  issue/notice@786139e592c7  Issued notice
      ├─ derived_from  issue/info_card@2e60b7baf5ac  Issued info_card
      ├─ derived_from  issue/emergency@3f0909c25c71  Issued emergency
      ├─ derived_from  issue/notice@81ba56f8d912  Issued notice
      ├─ derived_from  issue/info_card@937dc1bf1bd0  Issued info_card
      ├─ derived_from  issue/emergency@c15c760aabf6  Issued emergency
      ├─ informed_by  section/history.full@1
      └─ informed_by  section/safety.full@1
… closure truncated at 200 nodes

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

3927 with DOI

1 strong · 31 moderate · 7 weak

Compilations

12026-04-24T09:55:01.077Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09 · 1 other run

Decisions

44last ruled 2026-06-04

0 awaiting a ruling

Issued documents

62026-10-19T20:30:15.215Z

notice · info card · emergency

Searches

160 with no results

queries and counts on the build

Claims checked

8852 supported

52 supported · 36 not

Correspondence

0received

consent field ships in Phase 4

Edges

291

derivations recorded for this entity

Complete over 39 sources, 1 compilation, and 44 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/5-meo-dmt/archive

2Build

one panel per compilation run

generation run 2026-04-24

95 min completedmodel pipeline-v5plan not recordedrun/3fa9f3bc…

Selection

results seen80

selected by the model38

consumed as sources39

Verification

claims checked88

supported48

partially supported4

not supported1

inconclusive35

record
seen / partial
working

The model's own caveats

none raised on this run

Reproduce

inputs: 39 source keys (listed under Sources)
plan: not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model: pipeline-v5
streams: none — agent transcripts are persisted from 2026-09 onward

16 searches — query, source, results, what was kept and why

16 searches for this run
#	source	query	seen	kept	rationale
1	PubMed	5-methoxy-N,N-dimethyltryptamine Bufo alvarius toad venom psychedelic	3	2	Key sources for use patterns and toad venom context
2	PubMed	5-MeO-DMT GH001 treatment-resistant depression clinical trial	1	1	Key clinical trial publication
3	PubMed	5-methoxy-N,N-dimethyltryptamine metabolism monoamine oxidase MAO cytochrome	6	6	Core metabolism and drug interaction data
4	PubMed	5-MeO-DMT human study subjective effects pharmacokinetics clinical	2	2	Direct human PK/PD data
5	PubMed	5-MeO-DMT 5-methoxy-N,N-dimethyltryptamine pharmacology receptor binding	15	5	Most directly relevant to receptor pharmacology and mechanism of action
6	OpenAlex	5-MeO-DMT 5-methoxy-dimethyltryptamine psychedelic	10	1	Tyttarelli tryptamine review directly covers 5-MeO-DMT recreational use and toxicology
7	PubChem	5-MeO-DMT	1	1	Core chemical identity verification
8	ClinicalTrials.gov	5-MeO-DMT	10	8	All trials directly relevant to 5-MeO-DMT clinical development
9	PMC / WebFetch	PMC8902691 5-MeO-DMT narrative synthesis full text receptor binding PK	1	1	Comprehensive review; critical for pharmacology section
10	PubMed / Federal Register	5-MeO-DMT DEA Schedule I final rule	1	1	Official US legal scheduling record
11	WebSearch / Erowid / Wikipedia	5-MeO-DMT legal status UK Canada Australia Europe	10	3	International legal status coverage
12	WebSearch	5-MeO-DMT first synthesis Hoshino Shimodaira 1936 history	10	2	Historical data not available in PubMed
13	IUPHAR/BPS Guide to Pharmacology	5-MeO-DMT ligand ID 145 receptor binding	1	1	Primary source for verified receptor binding values; directly contradicts sigma-1 agonism in seed data
14	WebSearch / GH Research press release	GH001 NCT05800860 Phase 2b treatment resistant depression results	1	1	Clinical efficacy data for 5-MeO-DMT in TRD
15	IUPHAR/BPS GtoPdb vs PubMed receptor data	5-MeO-DMT receptor binding affinity cross-reference sigma-1 SERT	5	2	Critical cross-reference for seed data flags: sigma-1 agonism NOT supported; SERT binding low micromolar
16	Verify key DOIs via Crossref	Ermakova 2022, Reckweg 2022, Reckweg 2023 DOIs	3	1	Verification of primary clinical pharmacology references

88 claims by section — every cited sentence, checked against its source

safety27 · 16 ok

Animal LD₅₀ data reveal extreme species-specific variability:supported
LD50 data (sheep 1 mg/kg, mice 48-278 mg/kg) 02698811211050543
Claim in safety — inconclusiveinconclusiveworking →
Tryptamine intoxication can produce ataxia, tremor, convulsions, and respiratory failure at supratherapeutic exposures.supported
Covers 5-MeO-DMT adverse events and intoxication cases 1570159x13666141210222409
Claim in safety — inconclusiveinconclusiveworking →
5-MeO-DMT causes respiratory depression through 5-HT₁A-mediated inhibition of medullary respiratory neurons, as demonstrated in cat brainstem preparationssupported
5-MeO-DMT hyperpolarized respiratory neurons and reduced action potential discharges via 5-HT1A receptor activation; Documents respiratory depression mechanism pmid:7922531
Harmaline combination produces synergistic hyperthermia mediated through both 5-HT₁A and 5-HT₂A pathways — a serotonin toxicity mechanism that can be life-threatening.supported
Harmaline potentiates 5-MeO-DMT hyperthermia; both 5-HT1A and 5-HT2A involved; serotonin toxicity risk in combination use pmid:25446678
The Michaelis-Menten pharmacokinetics documented in mice mean that plasma exposure escalates non-proportionally with dosesupported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally dmd.111.039107
The most common challenging effects include intense fear, anxiety, panic, confusion, and overwhelming ego dissolutionsupported
subjective effects, benefits, and consequences associated with 5-MeO-DMT use 0269881118769063
The most common challenging effects include intense fear, anxiety, panic, confusion, and overwhelming ego dissolutionsupported
adverse effects 02698811211050543
Claim in safety — inconclusiveinconclusiveworking →
Persistent after-effects reported by a minority of users include flashbacks, insomnia, and persisting anxietysupported
consequences associated with 5-MeO-DMT use from synthetic, toad, and plant sources 0269881118769063
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The mechanism involves 5-HT₂A receptor down-regulation through receptor internalization and desensitizationpartially supported
5-HT2AR down-regulation in frontal cortex; beta-arrestin-2 independent acschemneuro.2c00170
In rodent models, tolerance to 5-HT₂A-mediated behavioral effects occurs within 24 hours of a single administration and is beta-arrestin-2-independentsupported
DOI induces rapid tolerance (24h) and cross-tolerance with LSD via 5-HT2A; beta-arrestin-2 independent acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Harmaline co-administration increases 5-MeO-DMT systemic exposure 3.6–4.4-fold and bufotenine levels 6–10-fold, producing combined serotonin toxicity manifesting as dangerous hyperthermia, seizures, and cardiovascular instabilitypartially supported
harmaline pretreatment raised 5-MeO-DMT exposure 3.6–4.4× and bufotenine 6–10× j.bcp.2010.02.020
Claim in safety — inconclusiveinconclusiveworking →
Harmaline co-administration increases 5-MeO-DMT systemic exposure 3.6–4.4-fold and bufotenine levels 6–10-fold, producing combined serotonin toxicity manifesting as dangerous hyperthermia, seizures, and cardiovascular instabilitypartially supported
Harmaline potentiates 5-MeO-DMT hyperthermia; both 5-HT1A and 5-HT2A involved; serotonin toxicity risk in combination use pmid:25446678
Claim in safety — inconclusiveinconclusiveworking →
A systematic review identified limited data on 5-MeO-DMT interactions with SSRIssupported
identified 2 studies on 5-MeO-DMT interactions; no serious adverse drug events except a few case reports 02698811231211219
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The quantified pharmacokinetic interaction (3.6–4.4× exposure increase) and documented serotonin toxicity risk place this combination in the highest-risk category.supported
harmaline pretreatment raised 5-MeO-DMT exposure 3.6–4.4× and bufotenine 6–10× j.bcp.2010.02.020
The quantified pharmacokinetic interaction (3.6–4.4× exposure increase) and documented serotonin toxicity risk place this combination in the highest-risk category.partially supported
serotonin toxicity risk in combination use pmid:25446678
Claim in safety — inconclusiveinconclusiveworking →
Respiratory compromise is a theoretical contraindication based on the demonstrated 5-HT₁A-mediated respiratory depression in animal models.supported
5-MeO-DMT hyperpolarized respiratory neurons and reduced action potential discharges via 5-HT1A receptor activation pmid:7922531

pharmacology18 · 11 ok

Psychedelic effects — indexed by head twitch response in rodent models, a behavioral correlate of hallucinogenic activity — are mediated primarily through 5-HT₂A receptor activationsupported
ED50 data for head twitch response (0.2–1.8 mg/kg); 5-HT1A agonism dampens 5-HT2A psychedelic-like effects acschemneuro.4c00513
Claim in pharmacology — inconclusiveinconclusiveworking →
Concurrent 5-HT₁A agonism significantly modulates the 5-HT₂A-driven response: 5-HT₁A activation suppresses or attenuates peak psychedelic intensity while contributing anxiolytic, antidepressant, and hypothermic effectssupported
5-HT1A agonism dampens 5-HT2A psychedelic-like effects acschemneuro.4c00513
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The 2025 cryo-EM structural study provided the first atomic-resolution view of 5-MeO-DMT bound within the 5-HT₁A receptor binding pocket, revealing conserved interaction motifs with the orthosteric site and confirming the structural basis for its antidepressant and anxiolytic activity relative to related bufotenine derivatives.supported
Cryo-EM structures of 5-HT1A bound to 5-MeO-DMT and bufotenine derivatives; 5-MeO-DMT retained strong antidepressant/anxiolytic effects; establishes molecular framework for 5-HT1A engagement research.0987
5-MeO-DMT also partitions into lipid bilayer membranes and crosses them spontaneously in molecular dynamics simulations, suggesting potential membrane-mediated pharmacological effects beyond canonical receptor bindingsupported
MD simulations: 5-MeO-DMT and DMT cross membranes spontaneously in neutral form; lipid bilayer partitioning may modulate receptor conformational equilibrium j.chemphyslip.2023.105279
Claim in pharmacology — inconclusiveinconclusiveworking →
Metabolism proceeds through two primary pathways:supported
CYP2D6 O-demethylates 5-MeO-DMT to bufotenine; MAO-A primarily inactivates it pmid:20942780
Metabolism proceeds through two primary pathways:supported
CYP2D6 identified as specific O-demethylase for 5-MeO-DMT (Km 12 uM, kcat 65 min-1) pmid:12777961
Claim in pharmacology — not_supportednot supportedworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
CYP2D6 poor metabolizers consequently produce less bufotenine, potentially altering the qualitative character of the subjective experiencesupported
CYP2D6 metabolizer status may affect 5-MeO-DMT experiences especially with MAOIs cpt.3459
Animal data provide the primary pharmacokinetic characterization:supported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally; brain concentrations also nonlinear dmd.111.039107
A safety-critical finding is nonlinear (Michaelis-Menten) pharmacokinetics at higher doses: AUC increases disproportionately with dose (1.5–2.7× higher than predicted by proportional scaling)supported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally; risk of intoxication increases disproportionately at higher doses dmd.111.039107
Co-administration with the MAO-A inhibitor harmaline increases systemic 5-MeO-DMT exposure by 3.6–4.4-fold and bufotenine exposure by 6–10-foldsupported
harmaline pretreatment raised 5-MeO-DMT exposure 3.6–4.4× and bufotenine 6–10× j.bcp.2010.02.020
Claim in pharmacology — inconclusiveinconclusiveworking →
This pharmacokinetic potentiation produces dangerous hyperthermia mediated through both 5-HT₁A and 5-HT₂A activation — a serotonin toxicity mechanism.supported
Harmaline potentiates 5-MeO-DMT hyperthermia; both 5-HT1A and 5-HT2A involved; serotonin toxicity risk in combination use pmid:25446678

summary12 · 7 ok

Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Psychedelic effects are 5-HT₂A-mediated; concurrent 5-HT₁A activation attenuates peak intensity while contributing anxiolytic and antidepressant propertiessupported
5-HT1A agonism dampens 5-HT2A psychedelic-like effects acschemneuro.4c00513
Metabolism proceeds through MAO-A N-deamination and CYP2D6 O-demethylation to the active metabolite bufotenine.supported
CYP2D6 O-demethylates 5-MeO-DMT to bufotenine; MAO-A primarily inactivates it pmid:20942780
The subjective experience is dominated by rapid, intense ego dissolution and mystical-type states — 75% of participants report complete mystical experiences at vaporized dosessupported
75% had complete mystical experience; no difference vs high-dose psilocybin fpsyg.2018.02459
No human lethal dose has been established; animal LD₅₀ values range from 1 mg/kg in sheep to 278 mg/kg in micesupported
LD50 data (sheep 1 mg/kg, mice 48-278 mg/kg) 02698811211050543
Pharmacokinetics are nonlinear — AUC increases 1.5–2.7× beyond proportional scaling at higher doses, creating disproportionate intoxication risksupported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally; risk of intoxication increases disproportionately at higher doses dmd.111.039107
The most critical drug interaction involves MAO inhibitors: harmaline co-administration increases systemic exposure 3.6–4.4-fold and bufotenine levels 6–10-fold, producing serotonin toxicity risksupported
harmaline pretreatment raised 5-MeO-DMT exposure 3.6–4.4× and bufotenine 6–10× j.bcp.2010.02.020
Claim in summary — inconclusiveinconclusiveworking →
Tolerance develops rapidly via 5-HT₂A receptor internalizationsupported
DOI induces rapid tolerance (24h) and cross-tolerance with LSD via 5-HT2A; 5-HT2AR down-regulation in frontal cortex acschemneuro.2c00170

pharmacokinetic-detail6 · 3 ok

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
All animal PK data are from Shen et al. 2011supported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally; brain concentrations also nonlinear dmd.111.039107
At higher doses, 5-MeO-DMT exhibits Michaelis-Menten (saturable) pharmacokinetics: AUC increases 1.5–2.7× more than predicted by dose-proportional scalingsupported
Nonlinear (Michaelis-Menten) PK in mice at high doses; AUC increased nonproportionally dmd.111.039107
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Inhibition of this pathway by harmaline produces dramatic pharmacokinetic potentiation:supported
harmaline pretreatment raised 5-MeO-DMT exposure 3.6–4.4× and bufotenine 6–10× j.bcp.2010.02.020
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

chemistry4 · 2 ok

O-demethylation of 5-MeO-DMT yields bufotenine (5-hydroxy-DMT), a metabolically and pharmacologically significant transformation catalyzed by CYP2D6.supported
CYP2D6 identified as specific O-demethylase for 5-MeO-DMT (Km 12 uM, kcat 65 min-1) pmid:12777961
Claim in chemistry — inconclusiveinconclusiveworking →
The succinate salt was developed to address pharmaceutical formulation requirements, providing improved handling and storage characteristics over the freebasesupported
1:1 succinate salt API (99.86% purity, 49% yield, 136g); solid-state characterization (XRPD, TGA, DSC, NMR); injectable formulation 20 mg/mL in sterile water acsomega.0c05099
Claim in chemistry — inconclusiveinconclusiveworking →

clinical-evidence4 · 4 ok

Preliminary antidepressant signals were noted.supported
safety and potential antidepressant effects fpsyt.2023.1133414
Full PK parameters were not reported in the abstract.supported
Phase 1 SAD trial of intranasal 5-MeO-DMT benzoate (BPL-003); safety, tolerability, PK, and altered states of consciousness 02698811241246857
A single real-world longitudinal case study documented 5-MeO-DMT administration for PTSDsupported
First longitudinal case study: single vaporized bufotoxin dose (est. 10-15 mg 5-MeO-DMT) in 23-year-old female with chronic PTSD fpsyt.2023.1271152
A separate prospective study documented reductions in salivary cortisol and IL-6 following synthetic 5-MeO-DMT inhalation, suggesting neuroendocrine and anti-inflammatory effects.supported
Prospective study of synthetic inhaled 5-MeO-DMT: reduced cortisol, reduced salivary IL-6 (anti-inflammatory) s00213-019-05414-w

comparative-pharmacology4 · 2 ok

5-MeO-DMT occupies a unique position among classical psychedelics: it produces the shortest-duration full psychedelic experience when vaporized (20–40 minutes total vs 4–6 hours for psilocybin, 8–12 hours for LSD)supported
Comparative review of psilocybin, LSD, DMT, 5-MeO-DMT, mescaline pharmacology, PKs, safety; no differences in psychedelic effects beyond duration j.bpsc.2024.01.007
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Values for DMT, psilocin, and LSD compiled from Ray 2010 and comparative reviewsupported
Comparative review of psilocybin, LSD, DMT, 5-MeO-DMT, mescaline pharmacology, PKs, safety j.bpsc.2024.01.007
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

neuroscience4 · 3 ok

Claim in neuroscience — inconclusiveinconclusiveworking →
The concurrent 5-HT₁A agonism distinguishes 5-MeO-DMT's neural signature from more 5-HT₂A-selective psychedelics. 5-HT₁A activation in the raphe nuclei provides autoreceptor-mediated inhibition of serotonergic firing, potentially constraining the duration and intensity of cortical 5-HT₂A-driven effectssupported
5-HT1A agonism dampens 5-HT2A psychedelic-like effects acschemneuro.4c00513
The rapid 5-HT₂A tolerance development (receptor internalization within 24 hours) documented for classical psychedelics suggests that even brief exposure triggers receptor-level signaling changes.supported
DOI induces rapid tolerance (24h) and cross-tolerance with LSD via 5-HT2A; 5-HT2AR down-regulation in frontal cortex acschemneuro.2c00170
The brevity of the disruption — followed by rapid reconsolidation — may explain the pattern of lasting well-being improvements reported after single sessions.supported
single inhalation of vapor from dried toad secretion containing 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 s00213-019-05236-w

receptor-pharmacology4 · 3 ok

Comprehensive receptor binding data have been compiled across multiple sources.supported
receptor binding Ki data 02698811211050543
Comprehensive receptor binding data have been compiled across multiple sources.supported
5-MeO-DMT primarily agonist at 5-HT1A and 5-HT2A (5-HT1A affinity highest) jnc.15587
Comprehensive receptor binding data have been compiled across multiple sources.supported
Radioligand binding: all 5-MeO-tryptamines showed selectivity for 5-HT1AR over 5-HT2AR; SERT interaction confirmed s41380-024-02506-8
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

history3 · 1 ok

Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The final rule was published in the Federal Register on December 20, 2010, and 5-MeO-DMT became a Schedule I Controlled Substance effective January 19, 2011supported
DEA final rule placing 5-MeO-DMT (including salts, isomers) into Schedule I of the CSA. Effective January 19, 2011. pmid:21171485

effects-overview2 · 0 ok

Claim in effects-overview — inconclusiveinconclusiveworking →
Claim in effects-overview — inconclusiveinconclusiveworking →

Other runs

brief run2026-09-27completed2 minrun/770d0239…

3Sources

39 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
year	source	tier	status	feeds
2026	Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept TrialSeynaeve M, Dunbar F, Hindocha C, Ermakova AO, Pierce M, Conley RR, Roberts C · CNS Drugsdoi:10.1007/s40263-025-01250-z	moderate	consumed	1 section
2025	Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of DepressionRamaekers JG, Reckweg JT, Mason NL · American Journal of Psychiatrydoi:10.1176/appi.ajp.20230890	moderate	consumed	cited only
2025	Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted TherapyHalman A, Conyers R, Moore C, et al. · Clinical Pharmacology and Therapeuticsdoi:10.1002/cpt.3459	moderate	consumed	1 section
2025	Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and AnxietyLi SJ, Yuan QN, Wu WY, et al. · Research (Washington, D.C.)doi:10.34133/research.0987	moderate	consumed	1 section
2024	5-MeO-DMT synthesis history and physical propertiesVarious web sources (Wikipedia, ResearchGate)url:414e2dfdcbd7f4bd	weak	consumed	cited only
2024	Drug-drug interactions involving classic psychedelics: A systematic reviewHalman A, Kong G, Sarris J, Perkins D · Journal of Psychopharmacologydoi:10.1177/02698811231211219	strong	consumed	1 section
2024	GH Research Phase 2b Trial Results: GH001 in Treatment-Resistant DepressionGH Research PLC / Psychiatric Timesurl:2a8b4b20aa361b94	weak	consumed	cited only
2024	IUPHAR/BPS Guide to Pharmacology — 5-MeO-DMT Ligand ActivityIUPHAR/BPS Curatorsurl:7f34d9a22c0f2896	weak	consumed	cited only
2024	Legal status of 5-MeO-DMT by jurisdictionErowid, Behold Retreats, Wikipediaurl:b6a62df3f5c55d24	weak	consumed	cited only
2024	Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participantsRucker JJ, Roberts C, Seynaeve M, et al. · Journal of Psychopharmacologydoi:10.1177/02698811241246857	moderate	consumed	1 section
2024	Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding ProfileHolze F, Singh N, Liechti ME, D'Souza DC · Biological Psychiatry: Cognitive Neuroscience and Neuroimagingdoi:10.1016/j.bpsc.2024.01.007	moderate	consumed	1 section
2024	Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-N,N-dimethyltryptamine Analogs in MiceGlatfelter GC, Clark AA, Cavalco NG, et al. · ACS Chemical Neurosciencedoi:10.1021/acschemneuro.4c00513	moderate	consumed	3 sections
2024	Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory propertiesPuigseslloses P, Nadal-Gratacos N, Ketsela G, et al. · Molecular Psychiatrydoi:10.1038/s41380-024-02506-8	moderate	consumed	3 sections
2024	Usona Institute NCT05698095: IM 5-MeO-DMT Phase 1 PK StudyUsona Instituteurl:f0ea686fb8fce3db	weak	consumed	cited only
2023	5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case studyRagnhildstveit A, Khan R, Seli P, Bass LC, August RJ · Frontiers in Psychiatrydoi:10.3389/fpsyt.2023.1271152	weak	consumed	2 sections
2023	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 depressionReckweg JT, van Leeuwen CJ, Henquet C, et al. · Frontiers in Psychiatrydoi:10.3389/fpsyt.2023.1133414	moderate	consumed	3 sections
2023	Interaction of psychedelic tryptamine derivatives with a lipid bilayerZohairi F, Khandelia H, Hakami Zanjani AA · Chemistry and Physics of Lipidsdoi:10.1016/j.chemphyslip.2023.105279	moderate	consumed	1 section
2023	Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptorsVargas MV, Dunlap LE, Dong C, Carter SJ, Tombari RJ, et al. · Sciencedoi:10.1126/science.adf0435	moderate	consumed	cited only
2022	A narrative synthesis of research with 5-MeO-DMTErmakova AO, Dunbar F, Rucker J, Johnson MW · Journal of Psychopharmacologydoi:10.1177/02698811211050543	moderate	consumed	7 sections
2022	The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)Reckweg JT, Uthaug MV, Szabo A, Davis AK, Lancelotta R, Mason NL, Ramaekers JG · Journal of Neurochemistrydoi:10.1111/jnc.15587	moderate	consumed	3 sections
2022	Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Micede la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · ACS Chemical Neurosciencedoi:10.1021/acschemneuro.2c00170	moderate	consumed	3 sections
2020	Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgmentUthaug MV, Lancelotta R, Szabo A, Davis AK, Riba J, Ramaekers JG · Psychopharmacologydoi:10.1007/s00213-019-05414-w	moderate	consumed	1 section
2020	Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical UseSherwood AM, Claveau R, Lancelotta R, Kaylo KW, Lenoch K · ACS Omegadoi:10.1021/acsomega.0c05099	moderate	consumed	1 section
2019	A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptomsUthaug MV, Lancelotta R, van Oorsouw K, Kuypers KPC, Mason N, et al. · Psychopharmacologydoi:10.1007/s00213-019-05236-w	moderate	consumed	1 section
2019	Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effectsSepeda ND, Clifton J, Doyle LY, Lancelotta R, Griffiths RR · Journal of Psychedelic Studiesurl:fe9db4ee5125b139	weak	consumed	cited only
2018	Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin StudyBarsuglia J, Davis AK, Palmer R, Lancelotta R, Windham-Herman AM, et al. · Frontiers in Psychologydoi:10.3389/fpsyg.2018.02459	moderate	consumed	1 section
2018	The epidemiology of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumptionDavis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E · Journal of Psychopharmacologydoi:10.1177/0269881118769063	moderate	consumed	1 section
2015	Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptorsJiang XL, Shen HW, Yu AM · Neuropharmacologypmid:25446678	moderate	consumed	2 sections
2015	Recreational use, analysis and toxicity of tryptamines.Tittarelli R, Mannocchi G, Pantano F, Romolo FS · Current neuropharmacologydoi:10.2174/1570159x13666141210222409	moderate	consumed	cited only
2013	Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 statusJiang XL, Shen HW, Mager DE, Yu AM · Drug Metabolism and Dispositiondoi:10.1124/dmd.112.050724	moderate	consumed	3 sections

Show all 39 sources — 9 more

Sources 31 to 39
year	source	tier	status	feeds
2011	Nonlinear pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine in miceShen HW, Jiang XL, Yu AM · Drug Metabolism and Dispositiondoi:10.1124/dmd.111.039107	moderate	consumed	4 sections
2010	Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokineticsShen HW, Wu C, Jiang XL, Yu AM · Biochemical Pharmacologydoi:10.1016/j.bcp.2010.02.020	moderate	consumed	4 sections
2010	Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actionsShen HW, Jiang XL, Winter JC, Yu AM · Current Drug Metabolismpmid:20942780	moderate	consumed	2 sections
2010	Psychedelics and the human receptoromeRay TS · PLoS ONEdoi:10.1371/journal.pone.0009019	moderate	consumed	cited only
2010	Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule.Drug Enforcement Administration · Federal Registerpmid:21171485	moderate	consumed	1 section
2008	Indolealkylamines: biotransformations and potential drug-drug interactionsYu AM · The AAPS Journaldoi:10.1208/s12248-008-9028-5	moderate	consumed	2 sections
2003	Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylaseYu AM, Idle JR, Herraiz T, Kupfer A, Gonzalez FJ · Pharmacogeneticspmid:12777961	moderate	consumed	2 sections
1994	Bufo alvarius: a potent hallucinogen of animal originWeil AT, Davis W · Journal of Ethnopharmacologypmid:8170151	moderate	consumed	2 sections
1994	The excitability and rhythm of medullary respiratory neurons in the cat are altered by the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamineLalley PM · Brain Researchpmid:7922531	moderate	consumed	1 section

4Docket

one filing per activity — decisions, correspondence, reports

0012026-04-24revisionRevision 1
Initial LLM generation (v5 pipeline, wiki)
psx:substance/5-meo-dmt/version/1
0022026-06-04proposal41 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
41 items in this filing
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- timeline · vaporized · onset
- timeline · vaporized · come_up
- timeline · vaporized · peak
- timeline · vaporized · resolution
- timeline · vaporized · afterglow
- timeline · insufflated · onset
- timeline · insufflated · come_up
- timeline · insufflated · peak
- timeline · insufflated · plateau
- timeline · insufflated · resolution
- timeline · insufflated · afterglow
- toxicity
- dependence · full
- withdrawal
- tolerance
- dosage · vaporized
- dosage · insufflated
- duration · vaporized · onset
- duration · vaporized · come_up
- duration · vaporized · peak
- duration · vaporized · offset
- duration · vaporized · total
- duration · vaporized · aftereffects
- duration · insufflated · onset
- duration · insufflated · come_up
- duration · insufflated · peak
- duration · insufflated · offset
- duration · insufflated · total
- duration · insufflated · aftereffects
- contraindication · other
- contraindication · psychiatric
- contraindication · psychiatric
- contraindication · cardiovascular
- contraindication · respiratory
- contraindication · pregnancy_breastfeeding
- contraindication · neurological
psx:substance/5-meo-dmt/proposal/dose_tier/57598476-6d86-4d94-aadf-9973669503cf
0032026-06-04publicationPublication — backfill
psx:substance/5-meo-dmt/pub/93159458-c861-4065-b1d0-4508b7fc3c2d
0042026-09-27revisionr1.a1
brief-overview retired 2026-09-30 (founder): Description reads the essential summary for every substance.
psx:substance/5-meo-dmt/version/2

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
document	content hash	issued	from version	superseded
emergency	c15c760aabf6f0fcf5b6fc6b…	2026-10-19 20:30	Revision 1	current
info_card	937dc1bf1bd08b19611da73b…	2026-10-19 20:30	Revision 1	current
notice	81ba56f8d912e57419b23b6c…	2026-10-19 20:30	Revision 1	current
emergency	3f0909c25c714d225b4bb3e3…	2026-09-04 04:28	Revision 1	superseded2026-10-19
info_card	2e60b7baf5ac45ea1dbc8128…	2026-09-04 04:28	Revision 1	superseded2026-10-19
notice	786139e592c77daa0f14b8ed…	2026-09-04 04:28	Revision 1	superseded2026-10-19

5-MeO-DMT

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