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Molecule guide

5-MeO-DMT: what the research shows

A very short-acting psychedelic, now in phase 3 as a nasal spray and inhaled treatment for depression. What trials found and how strong the evidence is.

ReviewedLast updated September 25, 2026

Also known as Mebufotenin, BPL-003 (nasal spray), GH001 (inhaled), Toad venom / 'Bufo'

At a glance

Type
Short-acting psychedelic tryptamine. Found in some plants and in the secretion of the Sonoran Desert toad. Not the same as DMT.
How it acts
Activates serotonin receptors, with strongest affinity for 5-HT1A as well as action at 5-HT2A.
Approved uses
None. Two pharmaceutical forms are in late-stage trials for treatment-resistant depression.
Legal status
Schedule I in the US since 2011. Not specifically listed under Canada's Controlled Drugs and Substances Act, but it can't legally be sold for human use.
How it's given in research
A nasal spray (BPL-003) or inhaled vapour (GH001) in clinic. The main effects are over in well under two hours.
Strongest evidence
Treatment-resistant depression, from one peer-reviewed randomised trial and a larger company-reported trial.
Biggest open question
Whether large phase 3 trials confirm the early results, and how long benefits last.

Evidence by condition

How strong the research is for each use, on our four-level evidence scale.

Treatment-resistant depression Moderate

An 81-person randomised trial of inhaled GH001 found a large drop in depression scores at day 8, with 57.5% in remission compared with 0% on placebo. A 193-person company-reported trial of the BPL-003 nasal spray also beat a low-dose control. Both are moving to phase 3.

Alcohol use disorder Very low

An open-label pilot of 12 people found fewer drinking days after one dose of BPL-003 alongside therapy. There was no control group.

Depression and anxiety (outside clinical trials) Very low

Surveys and naturalistic studies of people using 5-MeO-DMT in group or ceremonial settings report improvements. These are self-reports without controls.

What it is

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine, also called mebufotenin) is a naturally occurring psychedelic. It’s found in several plants and in large amounts in the secretion of the Sonoran Desert toad, Incilius alvarius (formerly Bufo alvarius).7 Plants containing it have a long history of ritual use.7 The toad secretion was first documented as psychoactive when smoked in 1994.12

Its effects are extremely intense but very brief. Taken as a nasal spray, blood levels peak within about 10 minutes, and the drug is cleared from the blood within about half an hour.3 People often describe a complete loss of the sense of self. That short duration is what has drawn drug developers to it: a treatment session could fit inside an ordinary clinic visit.

How it works in the brain

5-MeO-DMT activates serotonin receptors. Unlike most classic psychedelics, it has its highest affinity for the 5-HT1A receptor, alongside the 5-HT2A receptor that psilocybin and LSD mainly target.7 Compared with classic psychedelics, it tends to cause fewer visual effects and more ego dissolution.7

The medicines in development

Two pharmaceutical forms of synthetic 5-MeO-DMT are furthest along. Both target treatment-resistant depression.

BPL-003 nasal spray (AtaiBeckley)

BPL-003 was developed by Beckley Psytech, which combined with atai Life Sciences to form AtaiBeckley in November 2025.18

  • Phase 1, 2024: In 44 healthy volunteers, single doses up to 12 mg were well tolerated. The most common side effects were nasal discomfort, nausea, headache and vomiting.3
  • Phase 2a, 2026: In an open-label study of 12 people with treatment-resistant depression, one 10 mg dose was followed by an average 12–13 point drop in depression scores that lasted through 12 weeks. Most participants were ready to go home about 90 minutes after dosing.4
  • Phase 2b, 2025: In a 193-person randomised trial, single doses of 8 mg and 12 mg reduced depression scores more than a 0.3 mg control dose at every time point through week 8. At day 29, scores fell by 11.1 points on 12 mg versus 5.8 on the control.6 These results come from a company announcement and haven’t yet been published in a peer-reviewed journal.
  • Phase 3: After meeting with the FDA, the company planned two parallel phase 3 trials (ReConnection-1 and ReConnection-2), starting in the second quarter of 2026, with results expected in early 2029. BPL-003 has FDA Breakthrough Therapy designation.15

GH001 inhaled (GH Research)

  • Phase 1/2, 2023: In 16 people with treatment-resistant depression, an individualised dosing regimen, with up to three increasing inhaled doses on one day, led to remission at day 7 in 7 of 8 participants in that group.2
  • Phase 2b, 2026: In a randomised, double-blind trial at 16 European sites, 81 people received GH001 or placebo on a single day. By day 8, depression scores had dropped 15.5 points more with GH001. 57.5% were in remission, compared with 0% on placebo. No severe or serious adverse events were reported in that period.1
  • Regulatory: A US clinical hold placed in 2023 was lifted in January 2026, and the company plans global phase 3 trials.17

Other research

  • Alcohol use disorder: In an open-label pilot, 12 people received one 10 mg dose of BPL-003 within a 10-week therapy program. At 12 weeks, abstinent days had risen from 33% to 81% on average, and half the participants were continuously abstinent. There was no control group.5
  • Naturalistic use: In a survey of 515 people who had used 5-MeO-DMT, most reported strong mystical-type experiences. Of those with psychiatric diagnoses, most reported improvement, and few reported problems.9 A study of 42 people inhaling toad secretion at European retreats found lower depression, anxiety and stress scores four weeks later.10 These studies rely on self-selected participants and self-report.

Safety and risks reported in research

In clinical trials, common side effects were nasal discomfort (for the spray), nausea, headache and vomiting. Temporary rises in blood pressure were also reported.345 In the 12-person depression study, one person had a severe rise in blood pressure that returned to normal during observation.4

  • Canada: Canadian legal commentators note that 5-MeO-DMT isn’t specifically listed under the Controlled Drugs and Substances Act (DMT is, in Schedule III). But no product is authorised, and it can’t legally be sold for human use under the Food and Drugs Act.14
  • United States: Schedule I since January 2011.13 BPL-003 has Breakthrough Therapy designation.15
  • Conservation: Demand for toad secretion is linked to poaching of the Sonoran Desert toad.16

History in brief

  • Long history: Plants containing 5-MeO-DMT used in ritual settings.7
  • 1994: Toad secretion documented as psychoactive when smoked.12
  • 2011: US places 5-MeO-DMT in Schedule I.13
  • 2018–2019: First surveys and naturalistic studies of its effects.910
  • 2023: GH001 phase 1/2 trial in treatment-resistant depression published.2
  • 2025: BPL-003 phase 2b results announced. atai and Beckley Psytech combine.618
  • 2026: GH001 phase 2b published in JAMA Psychiatry. US hold on GH001 lifted. BPL-003 phase 3 planned.11715

Myths vs evidence

The claim“5-MeO-DMT is just a stronger version of DMT.”

What the evidence says Misleading

They're related tryptamines, but they act differently. 5-MeO-DMT has its highest affinity for the 5-HT1A serotonin receptor. It tends to produce fewer visual effects and higher rates of ego dissolution than classic psychedelics.7

The claim“Because it's short, 5-MeO-DMT is gentle.”

What the evidence says Misleading

Its effects are brief but extremely intense. Some people later experience sudden 'reactivations', a re-experiencing of the drug's effects days or weeks afterwards, which is less common with other psychedelics.118

The claim“Toad-derived 5-MeO-DMT is more natural, so it's better.”

What the evidence says Unproven

There's no evidence toad secretion works better than the pure compound. It varies in strength, contains other substances, and demand for it is linked to poaching of the Sonoran Desert toad.16 The medicines in trials use synthetic 5-MeO-DMT.

See all myths vs evidence →

Frequently asked questions

What is the difference between 5-MeO-DMT and DMT?

Both are tryptamine psychedelics with very short effects, but they're different molecules with different effects. DMT is the main active compound in ayahuasca and acts mainly on serotonin 2A receptors. 5-MeO-DMT acts strongly on 5-HT1A receptors, tends to produce fewer visuals, and is often described as overwhelming or all-encompassing.

What are BPL-003 and GH001?

They're two pharmaceutical forms of 5-MeO-DMT (also called mebufotenin) in development for treatment-resistant depression. BPL-003 is a nasal spray developed by Beckley Psytech, now part of AtaiBeckley. GH001 is an inhaled form developed by GH Research. Neither is approved yet.

Why does the short duration matter?

Psilocybin and LSD sessions take most of a day. In BPL-003 trials, most participants were ready to go home about an hour and a half after dosing.4 If approved, that could make treatment much easier to fit into an ordinary clinic visit.

Is 5-MeO-DMT legal in Canada?

It's a grey area. Canadian legal commentators note that 5-MeO-DMT isn't specifically listed under the Controlled Drugs and Substances Act, unlike DMT. However, no product is authorised, and selling it for human consumption isn't legal under the Food and Drugs Act. Talk to a qualified health professional about your own situation.

Clinical trials

Showing 2 of 2 active trials in our tracker.

See all trials in the tracker →

References

  1. Cubała WJ, et al. GH001 vs placebo in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2026;83(6):561–569. Source
  2. Reckweg JT, et al. 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. Frontiers in Psychiatry. 2023;14:1133414. Source
  3. Rucker JJ, et al. 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. Journal of Psychopharmacology. 2024;38(8):712–723. Source
  4. Roberts C, et al. A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression. Journal of Psychopharmacology. 2026;40(8):1247–1260. Source
  5. Marsden J, et al. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) for alcohol use disorder: an open-label, phase 2, proof-of-concept, clinical trial. Addiction. 2025. Published online December 10, 2025. Source
  6. atai Life Sciences and Beckley Psytech. Positive topline results from the phase 2b study of BPL-003 in patients with treatment-resistant depression. Company announcement, 2025. Source
  7. Ermakova AO, et al. A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology. 2022;36(3):273–294. Source
  8. Dourron HM, et al. 5-MeO-DMT: an atypical psychedelic with unique pharmacology, phenomenology & risk? Psychopharmacology. 2025;242(7):1457–1479. Source
  9. Davis AK, et al. The epidemiology of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) use: benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of Psychopharmacology. 2018;32(7):779–792. Source
  10. Uthaug MV, et al. 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. Psychopharmacology. 2019;236(9):2653–2666. Source
  11. Ortiz Bernal AM, et al. Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: an initial exploratory analysis of the phenomenon's predictors and its emotional valence. Frontiers in Psychiatry. 2022;13:1049643. Source
  12. Weil AT, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. Journal of Ethnopharmacology. 1994;41(1–2):1–8. Source
  13. Federal Register. Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule, December 20, 2010 (effective January 19, 2011). Source
  14. PsychedelicLaw.ca. Is 5-MeO-DMT (Bufo) legal in Canada? Source
  15. AtaiBeckley. BPL-003 phase 3 program initiation on track for Q2 2026 following successful FDA end-of-phase 2 meeting. Company announcement, March 10, 2026. Source
  16. National Geographic. The Sonoran Desert toad can get you high. Poachers have taken notice. Source
  17. GH Research. FDA lifts clinical hold on GH001, clearing path for global phase 3 initiation in 2026. Company announcement, January 5, 2026. Source
  18. atai Life Sciences and Beckley Psytech. Successful completion of their strategic combination to create AtaiBeckley. Company announcement, November 5, 2025. Source