5-MeO-DMT (Tryptamine · Potent Serotonergic · Research Reference)
| Compound | 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT; O-Methyl-bufotenin) |
| Class | Alkaloid — Tryptamine (Indole) |
| CAS | 1019-45-0 |
| Molecular formula | C₁₃H₁₈N₂O |
| Primary sources | Virola theiodora (bark resin), Anadenanthera colubrina (seeds, minor), Incilius alvarius (toad parotoid glands — non-plant) |
| Plant part | Bark resin, seeds |
| Claim strength | Emerging |
| Key applications | Psychedelic research; mystical experience induction; addiction research; informational-only |
| Buy from Herbuno | Informational reference — see HerbIQ Compound Index → |
Name origin: 5-MeO-DMT is the 5-methoxy analogue of DMT — the methoxy group at C-5 of the indole ring distinguishes it from bufotenin (5-hydroxy) and DMT (no C-5 substituent). The methoxy group enhances lipophilicity relative to bufotenin, dramatically improving blood-brain barrier penetration and potency — 5-MeO-DMT is approximately 4–6 times more potent than DMT on a mass basis. Traditional use: 5-MeO-DMT-containing plant preparations have been used in South American shamanic traditions — particularly Virola resin snuffs among the Yanomami and related peoples of the Amazon-Orinoco basin. Incilius alvarius toad venom (which contains ~15% 5-MeO-DMT dry weight) has been used in contemporary ceremonial contexts in Mexico and the US, though this represents a modern phenomenon rather than deep historical tradition. Research trajectory: 5-MeO-DMT has attracted significant clinical research attention — a single administration produces intense but brief (15–45 minutes smoked) mystical-type experiences with sustained antidepressant effects documented in observational studies. Multiple open-label trials and one small RCT have examined 5-MeO-DMT for treatment-resistant depression, PTSD, and end-of-life distress. Safety context: 5-MeO-DMT is Schedule I in the US (as of 2011), similarly controlled in most jurisdictions. Cardiovascular stimulation at high doses, and interactions with MAO inhibitors (potentially fatal serotonin syndrome), are the primary safety concerns.
Research Profile of 5-MeO-DMT
Serotonergic pharmacology: 5-MeO-DMT is a potent agonist at 5-HT1A and 5-HT2A receptors, with the 5-methoxy group shifting affinity toward 5-HT1A relative to DMT. This gives 5-MeO-DMT a pharmacologically distinct profile — the 5-HT1A component may contribute to its rapid antidepressant effects (analogous to buspirone) alongside the psychedelic 5-HT2A component. It also acts at sigma-1 and TAAR1 receptors. Claim strength: Moderate (mechanistic).
Antidepressant clinical evidence: A naturalistic survey of 5-MeO-DMT ceremonial use (Uthaug 2019, Psychopharmacology) showed significant reductions in depression and anxiety scales persisting 4 weeks post-session. A Phase II open-label trial (Davis et al.) demonstrated rapid antidepressant effects in adults with depression. A 2023 randomised controlled trial (Beckley Psytech / Nuada) showed significant antidepressant efficacy with synthetic 5-MeO-DMT versus placebo in treatment-resistant depression. These represent the most advanced clinical psychedelic data specifically for 5-MeO-DMT. Claim strength: Moderate (emerging clinical).
Addiction research: Observational data suggest 5-MeO-DMT ceremonial use is associated with reduced use of alcohol, opioids, and stimulants, consistent with the general psychedelic addiction-interruption hypothesis. No controlled trial data for addiction treatment are yet available for 5-MeO-DMT specifically. Claim strength: Emerging.
Drug interaction risk — MAO inhibitors: 5-MeO-DMT is metabolised primarily by MAO-A; co-administration with any MAO inhibitor (pharmaceutical antidepressants, beta-carbolines) produces dramatically elevated plasma 5-MeO-DMT levels and serotonin syndrome risk, including hyperthermia, seizures, and cardiovascular collapse. This is a life-threatening interaction requiring explicit clinical management. Claim strength: High (pharmacokinetic).
This compound is documented for research and formulator education purposes. For commercially available botanical ingredients, explore the HerbIQ Compound Index →
Regulatory and Research Context
5-MeO-DMT is Schedule I in the US (DEA scheduling effective January 2011), Class A in the UK, and controlled in most major jurisdictions. Research use requires Schedule I researcher registration. Several clinical research programmes are actively pursuing IND/CTA pathways for synthetic 5-MeO-DMT formulations (Beckley Psytech, GH Research).
The toad-secretion source (Incilius alvarius) raises significant wildlife conservation concerns — wild toad populations are being impacted by growing demand for milking ceremonies. Synthetic 5-MeO-DMT is pharmacologically identical to the toad-derived compound and is preferred for research and legal ceremonial use where jurisdictional exemptions exist.
No supplement, food, or cosmetic application. 5-MeO-DMT's potency (active at microgram quantities smoked) and drug interaction risk profile make it unsuitable for any uncontrolled consumer context.
This entry documents 5-MeO-DMT as part of the HerbIQ tryptamine psychedelic series. The clinical development trajectory is the most advanced of the three DMT-series compounds (DMT, bufotenin, 5-MeO-DMT) documented here.
Frequently Asked Questions — 5-MeO-DMT
How does 5-MeO-DMT differ from N,N-DMT experientially and pharmacologically?
Both are tryptamine psychedelics acting at 5-HT2A, but 5-MeO-DMT has greater 5-HT1A affinity and is 4–6 times more potent. Experientially, 5-MeO-DMT typically produces a more oceanic, ego-dissolving effect with less visual complexity than N,N-DMT, and a higher incidence of reported mystical-type experiences. Duration is similarly brief (15–45 minutes smoked). The 5-HT1A component may contribute to its observed rapid antidepressant effects independent of the full psychedelic experience.
Is Incilius alvarius toad sourcing sustainable?
No — milking of wild I. alvarius toads for ceremonial use has raised serious conservation concerns, with uncontrolled harvesting affecting wild populations in the Sonoran Desert (Arizona, New Mexico, northwestern Mexico). Conservation organisations and some regulatory bodies are advocating for bans on toad milking. Synthetic 5-MeO-DMT is chemically identical and ethically preferable for any research or legally permitted ceremonial use.
What is the MAO inhibitor interaction risk with 5-MeO-DMT?
MAO-A is the primary metabolic enzyme for 5-MeO-DMT. Any MAO inhibitor — pharmaceutical (phenelzine, tranylcypromine, moclobemide), dietary (harmala beta-carbolines from ayahuasca or Peganum harmala), or supplement (high-dose St John's Wort) — can dramatically increase 5-MeO-DMT plasma concentrations and cause serotonin syndrome. Fatalities have occurred from 5-MeO-DMT + MAOI combinations. This interaction is non-negotiable in any clinical or ceremonial context: MAOI washout periods must be confirmed.
Which pharmaceutical companies are developing synthetic 5-MeO-DMT?
GH Research (Ireland/US — GH001 programme for treatment-resistant depression, received FDA Breakthrough Therapy designation in 2021) and Beckley Psytech (UK — BPL-003 programme) are the primary clinical-stage developers of synthetic 5-MeO-DMT. Both use synthetic compound rather than toad-derived material. This regulatory trajectory positions 5-MeO-DMT as a possible future prescription psychiatric medication in coming years.
Related compounds: N,N-DMT, Bufotenin, Harmine, Ibogaine
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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