Skip to content

Mebufotenin

  • Prescription medicine
  • Not available
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Mebufotenin does in the body

Nothing approved. A synthetic inhaled version is in trials for depression that has not responded to other drugs; the substance itself is Schedule I

Inhaled as a vapour, the molecule reaches the brain in a few seconds because it goes straight from the lungs into arterial blood. It switches on serotonin receptors, with an unusually strong pull on the 5-HT1A subtype — a different balance from LSD or psilocybin, which favour 5-HT2A. The experience is overwhelming, very short, and often has no narrative content at all. Because monoamine oxidase destroys the molecule quickly, anything that inhibits that enzyme turns a 20-minute effect into a dangerous overdose; the one published death involved exactly that combination.

What happened in people

No change in cognition, mood or well-being measures in that same healthy-volunteer phase 1

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.

The limit that matters most

Harvesting Incilius alvarius secretion for ceremonial use is a conservation and animal-welfare pressure that the synthetic clinical formulation does not create

Where it acts
Cortical and limbic 5-HT1A and 5-HT2A receptors, reached within seconds of inhalation because the drug bypasses the gut and the liver entirely
Kind of result
Symptoms and quality of life
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · X0MKX3GWU9 · read 2026-08-29

Where each sentence above came from

The recorded explanation is written in label language rather than for a beginner. The page opens with what it is taken for instead, and the recorded explanation follows below.

Shown as the opening line on this page.

A limit recorded against this substance. Not signed off as a reviewed claim.

The four opening statements run to 129 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Placebo

A placebo is a dummy treatment given so the real one can be compared with it.

A picture of it, and where the picture fails

A placebo is like a blank control in an experiment.

Where that stops being true. A blank does nothing. People given a placebo often do get better.

What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.

An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.

Comparator

A comparator is whatever the treatment was measured against.

A picture of it, and where the picture fails

It is like the other runner in a race.

Where that stops being true. A race has one winner. A study can show both arms improved.

What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.

The control condition against which the experimental intervention is assessed.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Mean change in MADRS from baseline to day 7

The study showed what it set out to show

Who was studied
NCT05800860 (GH001 phase 2b, treatment-resistant depression)
How many people
81
Study design
Phase 2b randomised, double-blind, placebo-controlled with open-label extension
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Least-squares mean difference -15.5 versus placebo, effect size -2.0; remission (MADRS ≤ 10) at day 8 in 57.5% versus 0% on placebo
Repeated elsewhere
Unreplicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. A 0% placebo remission rate is far below the placebo response usual in depression trials and is consistent with complete functional unblinding, since the drug effect is unmistakable within seconds of inhalation. The trial was sponsored, designed and analysed by the manufacturer.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Vaporised inhalation, single supervised session, doses escalated within one day

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Safety (phase 1 part) and proportion in remission (MADRS ≤ 10) at day 7 (phase 2 part)

The study showed what it set out to show

Who was studied
NCT04698603 (GH001 phase 1/2, treatment-resistant depression)
How many people
16
Study design
Phase 1/2 open-label
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Remission at day 7 in 7/8 (87.5%) of the individualised-dosing group, p < 0.0001; 2/4 at 12 mg and 1/4 at 18 mg in the phase 1 part
Repeated elsewhere
Partially Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Open-label, no control arm, 16 patients in total with four per single-dose group. Funder involved in study design, data analysis and manuscript preparation, as disclosed.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Vaporised inhalation, single supervised session, doses escalated within one day

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

Safety, tolerability and dose-related psychoactive effects

The study showed what it set out to show

Who was studied
NCT04640831 (GH001-HV-101 phase 1, healthy volunteers)
How many people
22
Study design
Phase 1 dose-ranging
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Significant increases over 2 mg on PES, MEQ, EDI and 5D-ASC at 6, 12 and 18 mg; no significant change on the Challenging Experience Questionnaire
Repeated elsewhere
Unreplicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Cognition, mood and well-being measures were not affected by the drug in healthy volunteers — a null result that sits uneasily beside the naturalistic survey literature.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Vaporised inhalation, single supervised session, doses escalated within one day

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event No evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life No evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
  5. A number that stands in for health No evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals No evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
  8. Cells in a dish No evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Mebufotenin

    What a person takes: Vaporised inhalation, single supervised session, doses escalated within one day.

    The measurement behind this step

    The clinical formulation is vaporised and inhaled in a monitored session; the individualised regimen gives up to three increasing doses within a single day, which is possible only because the acute effect resolves in under half an hour. Naturalistic use is inhalation of vapour from synthetic freebase or from dried toad secretion of unknown composition.

  2. Getting in

    Inhaled as a vapour

    The dose is vaporised and drawn into the lungs. Taken by mouth on its own it does almost nothing, because gut and liver enzymes destroy it before it reaches the brain.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Vaporised freebase, 6 to 18 mg in the clinical programme. Pulmonary absorption delivers the molecule into arterial blood without first-pass metabolism; oral bioavailability is negligible because monoamine oxidase A in gut wall and liver deaminates it, which is why oral preparations pair it with an MAO inhibitor.

  3. Reaching the cell

    Reaches the brain in seconds

    Onset is faster than an intravenous injection because the blood goes lung to heart to brain. The full effect arrives before the person can put the device down.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Lipophilic tryptamine crossing the blood-brain barrier without a transporter. Time to peak subjective effect is under a minute by inhalation and the acute experience is largely over within 15 to 30 minutes, which is what makes a three-dose escalation within a single day feasible.

  4. What it acts on

    Activates 5-HT1A more strongly than 5-HT2A

    It binds serotonin receptors, but with a different balance from LSD or psilocybin — pulling harder on the subtype that quietens neurons than on the one that excites them.

    Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.

    The measurement behind this step

    Agonist at 5-HT1A with higher affinity than at 5-HT2A. 5-HT1A is Gi-coupled and inhibitory, 5-HT2A is Gq-coupled and excitatory; the inverted affinity ratio relative to the other classical psychedelics is the standard explanation for the qualitatively different, largely contentless experience, though no human study has separated the two receptors' contributions with an antagonist.

  5. The change it makes

    Destroyed by monoamine oxidase within minutes

    An enzyme in the body strips the molecule apart almost as fast as it arrives. That is why the experience is so short — and why blocking that enzyme is dangerous.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Oxidative deamination by MAO-A is the principal clearance route, with CYP2D6-mediated O-demethylation to bufotenin as a competing pathway. Harmaline and other MAO-A inhibitors raise and prolong exposure; the published fatality involved that combination.

  6. What that does for a person

    Depression scores fall within hours, in the trials

    In the phase 2b, more than half the treated group were in remission a week later, and most improvements were visible on day one. The drug itself was gone within the hour.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    MADRS remission at day 8 in 57.5% versus 0% on placebo, with remissions observed from day 1 and, in the earlier phase 1/2, six of ten remissions apparent from two hours. No mechanism links a 20-minute receptor exposure to a week-long change in mood ratings; the persistence is an observation, not an explanation.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • In the trials: adults with treatment-resistant depression, dosed once in a single supervised day. Outside the trials it is taken as a vapour, either synthetic or from dried toad secretion, in unregulated group ceremonies.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

Where the result stopped carrying

  • Phase 2 trials in postpartum depression (NCT05804708) and bipolar II disorder (NCT05839509) were both terminated, at enrolments of 10 and 6
  • The healthy-volunteer phase 1 found no effect on the mood and well-being measures it collected, despite a clear dose-response on experience intensity
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Not available

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Vaporised inhalation, single supervised session, doses escalated within one day

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

RNAWiki has not recorded a supervision or regulatory status for this substance.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

No register row and no identity class settled the question.

No source is stored against this line.

What is in the pack

The clinical formulation is vaporised and inhaled in a monitored session; the individualised regimen gives up to three increasing doses within a single day, which is possible only because the acute effect resolves in under half an hour.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold. The rest of the recorded wording: Naturalistic use is inhalation of vapour from synthetic freebase or from dried toad secretion of unknown composition.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

Acute effects are intense, begin within seconds and are largely over in 15 to 30 minutes. In the phase 1, vital signs at 1 and 3 hours were unaffected and adverse events were generally mild and self-resolving. The dominant documented hazard is pharmacokinetic: monoamine oxidase inhibitors, including prescribed MAOIs and harmala alkaloids in ayahuasca-style preparations, prolong and raise exposure and are implicated in the published fatality. Toad secretion additionally contains cardioactive bufadienolides. Delayed re-emergence of the experience without redosing, described in the literature as reactivation, is reported in naturalistic settings; its incidence is not established.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearNothing found in the sources checked

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Vaporised inhalation, single supervised session, doses escalated within one day

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Naturalistic use is inhalation of vapour from synthetic freebase or from dried toad secretion of unknown composition.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.

Questions worth asking

  • Which of the trials of Mebufotenin studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That the phase 2b effect size of -2.0 is pharmacological, when the placebo arm produced zero remissions and the drug reveals its allocation within seconds

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That retrospective self-ratings from ceremony attendees estimate an antidepressant effect size

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a 5-HT1A-weighted binding profile explains the qualitative difference from LSD or psilocybin — no human antagonist study has separated the receptors' contributions

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That toad-derived material and the synthetic clinical formulation are the same exposure; the secretion also contains bufotenin and cardioactive bufadienolides in undefined proportions

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How much did people take in the studies?

The sources RNAWiki checked hold nothing for this field.

Why it matters. A result belongs to an amount. Without the amount the result floats free.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

How fast does the body clear it?

The sources RNAWiki checked hold nothing for this field.

Why it matters. Without this, nothing on this page can say how long anything lasts.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Mebufotenin are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

Phase 2b: 15.5-point MADRS advantage and 57.5% remission against 0% on placebo
In plain words
In a randomised placebo-controlled trial of 81 people whose depression had not responded to at least two other drugs, a single day of inhaled doses put more than half into remission within a week. Nobody on placebo remitted.
What was measured
MADRS change from baseline to day 7 and remission rate at day 8, n=81
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NCT05800860 was a randomised, double-blind, placebo-controlled phase 2b with an open-label extension in 81 patients with treatment-resistant depression, completed March 2025. The primary endpoint was mean change in MADRS from baseline to day 7. A single-day individualised dosing regimen of GH001 produced a least-squares mean difference of -15.5 versus placebo, effect size -2.0, with 57.5% remission (MADRS ≤ 10) at day 8 against 0% on placebo. Forty patients received GH001 in the double-blind part. In the published post hoc analysis, remission at day 8 did not correlate with the number of prior antidepressant failures (r = -0.13, p = 0.44), and remission rates were 53.9% to 63.6% across subgroups defined by 2, 3, 4 or ≥5 prior failures. Three of the six authors of that analysis are employees of the sponsor.
Source
Thase ME et al. Psychopharmacol Bull 2026;56:8-21, reporting the NCT05800860 phase 2b result
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A 0% placebo remission rate is a signal about the blind, not only about the drug
In plain words
Not one person in the placebo group of the phase 2b reached remission. In depression trials, placebo response is normally large. A zero says the two groups could tell which one they were in.
What was measured
That a 15.5-point MADRS separation against a 0% placebo remission rate measures a drug effect rather than a drug effect plus a fully unblinded expectancy effect
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Across antidepressant trials, placebo remission at one week is routinely non-zero and placebo response rates in the 30% range are the usual reason drug-placebo separation is hard to demonstrate. A 0% placebo remission rate in a psychedelic trial is consistent with a group who knew they had received nothing: 5-MeO-DMT produces an unmistakable effect within seconds of inhalation, so allocation is revealed at the moment of dosing to participant and observer alike. The reported effect size of -2.0 therefore contains an expectancy component of unknown size that the design cannot isolate. This is a limitation shared by every trial in this file and is not a criticism of the conduct of this one; it is the reason the record does not treat -15.5 as a pharmacological effect size.
Source
NCT05800860 phase 2b design and result as reported in Thase ME et al. Psychopharmacol Bull 2026;56:8-21
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Dose-ranging in 22 healthy volunteers established the escalating single-day regimen
In plain words
A phase 1 gave 2, 6, 12 or 18 milligrams to healthy people. Higher doses produced stronger experiences, vital signs were unaffected, and stepping the dose up within one day produced the strongest effect of all.
What was measured
Dose-related change in PES, MEQ, EDI and 5D-ASC ratings, plus vital signs and cognition, n=22
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GH001-HV-101 gave single vaporised doses of 2 mg (n=4), 6 mg (n=6), 12 mg (n=4) and 18 mg (n=4), plus an individualised dose-escalation regimen (n=4), to 22 healthy volunteers. Doses of 6, 12 and 18 mg produced significant increases over 2 mg on the Peak Experience Scale, Mystical Experience Questionnaire, Ego Dissolution Inventory and 5D-ASC, but not on the Challenging Experience Questionnaire. Maximal ratings occurred with individualised escalation. Vital signs at 1 and 3 hours were unaffected and adverse events were generally mild and self-resolving. Measures of cognition, mood and well-being were not changed. That last finding is the one usually left out of summaries: the phase 1 found the experience scaled with dose and the psychological outcome measures did not move.
Source
Reckweg J et al. Front Pharmacol 2021;12:760671 (NCT04640831)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The one published death was a monoamine-oxidase interaction
In plain words
A man died after drinking a brew that combined 5-MeO-DMT with harmala alkaloids. The alkaloids block the enzyme that normally destroys the tryptamine within minutes, so a short experience became a lethal exposure.
What was measured
Postmortem 5-MeO-DMT and harmala alkaloid concentrations in a fatal case, with the pharmacokinetic interaction quantified separately
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sklerov et al. reported a fatal intoxication following ingestion of 5-MeO-DMT in an ayahuasca-style preparation, with harmala alkaloids identified in the material and in postmortem specimens. The mechanism is pharmacokinetic and reproducible: 5-MeO-DMT is deaminated by monoamine oxidase A, and Shen et al. demonstrated in a controlled system that the reversible MAO-A inhibitor harmaline raises and prolongs 5-MeO-DMT exposure, with CYP2D6 status modifying the effect through the competing O-demethylation pathway to bufotenin. This is the interaction that matters clinically, and it extends to prescribed MAO inhibitors. Inhalation without an MAO inhibitor gives an exposure lasting minutes; the same amount with one does not.
Source
Sklerov J et al. J Anal Toxicol 2005;29:838-841; Shen HW et al. Drug Metab Dispos 2013;41:975-986
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The naturalistic survey results describe who answered the survey
In plain words
Surveys of people who had used it in ceremonies report large improvements in depression and anxiety. Everyone in those samples chose to attend, chose to answer afterwards, and rated their own symptoms from memory.
What was measured
That retrospective self-ratings from self-selected ceremony attendees estimate an antidepressant or anxiolytic effect size
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Davis et al. surveyed 362 adults who had used 5-MeO-DMT in a naturalistic group setting and found self-reported improvement in depression and anxiety among those who reported having had those conditions, with improvement associated with the intensity of the mystical experience. Uthaug et al. followed participants at a single retreat and found reductions in self-rated depression, anxiety and stress alongside increased satisfaction with life. Neither has a control group, both recruit from people who sought the experience out, and the outcome is a retrospective self-rating collected in the setting that produced the experience. These studies establish that the effect is reported and that it is common enough to be worth a trial; they do not estimate its size, and the phase 1 in healthy volunteers found no change in mood or well-being measures at all.
Source
Davis AK et al. Am J Drug Alcohol Abuse 2019;45:161-169; Uthaug MV et al. Psychopharmacology 2019;236:2653-2666
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Scheduled in 2010 as having no medical use, in randomised trials by 2023
In plain words
The DEA put 5-MeO-DMT in Schedule I in December 2010. Thirteen years later a synthetic version of the same molecule was running placebo-controlled trials in depression under a name assigned by the WHO.
What was measured
Date of Schedule I placement versus registered trial phase for the same molecule
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DEA published the final rule placing 5-methoxy-N,N-dimethyltryptamine into Schedule I on 20 December 2010 (75 FR 79296), after proposed rules in August and October 2009. Schedule I requires a finding of no currently accepted medical use in the United States. GH Research began registered clinical trials of a vaporised synthetic formulation in 2020, completed a phase 1/2 in treatment-resistant depression in 2023 and a randomised placebo-controlled phase 2b in 2025, and the molecule now carries the international nonproprietary name mebufotenin. Two of the company's phase 2 trials, in postpartum depression (NCT05804708, n=10) and bipolar II disorder (NCT05839509, n=6), were terminated. The scheduling finding and the development programme coexist because they are made by different bodies against different standards.
Source
DEA final rule 75 FR 79296 (20 December 2010); ClinicalTrials.gov NCT05800860, NCT05804708, NCT05839509
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Two phase 2 trials in other indications were terminated
In plain words
The same company ran trials in postpartum depression and bipolar II depression. Both stopped early, with ten and six patients enrolled.
What was measured
Registered trial status and actual enrolment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NCT05804708, a phase 2 trial of GH001 in postpartum depression, is recorded on ClinicalTrials.gov as terminated with an actual enrolment of 10. NCT05839509, a phase 2 trial in bipolar II disorder, is recorded as terminated with an actual enrolment of 6. Neither has posted results. A terminated trial with single-digit enrolment produces no efficacy information in either direction, and the record notes them because a development programme summarised only by its completed trials is a filtered one.
Source
ClinicalTrials.gov NCT05804708 and NCT05839509, registry status records
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
X0MKX3GWU9
CAS registry number
1019-45-0
PubChem compound
1832
ChEBI
2086
WHO international nonproprietary name list entry
12325
EMA substance identifier
300000033352
European Chemicals Agency number
213-813-2
DrugBank
DB14010

Checks this page had to pass

  • Passed

    Identity resolved

    no open identity hold

  • Passed

    No unresolved merge across substance families

    no quarantine open

  • Passed

    Every public sentence names a source

    The opening statement carries the origin: Written into the record, not signed off.

  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

  • Passed

    No internal keys in reader text

    enforced by the copy-contract test over the rendered page

  • Not passed

    Safety mode resolved

    No register row and no identity class settled the question.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

7 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

  • What was measured, goal by goal — found nothing in the sources checked.
  • Felt, measured, or meaningful — found nothing in the sources checked.
  • How long anything takes — found nothing in the sources checked.
  • What it may clash with — found nothing in the sources checked.
  • Other ways to the same goal — found nothing in the sources checked.
  • How this medicine reached us — found nothing in the sources checked.
  • What changed on this page — found nothing in the sources checked.

The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

The fastest and shortest-acting classical psychedelic — effects begin in seconds and are over in half an hour — and a randomised placebo-controlled phase 2b in 81 patients reported a 15.5-point MADRS advantage and 57.5% remission at day 8 against 0% on placebo, in a trial that could not be blinded and was designed and analysed by the sponsor.

Recorded evidence blocks (7)

What did Mebufotenin's largest trial (81 people) and its longest (2.2 years) measure?


81 people in Mebufotenin's largest registered study, 2.2 years in its longest registered window, measuring Maximum Plasma Concentration (Cmax) following sublingual administration of 5-MeO-DMT. ClinicalTrials.gov · 2026-09-01

8 phase1, 6 phase2; NCT06810765; 2027-12; no ageing endpoint recorded. Last human test completed 2025, NCT05800860.

Interpretation These counts include studies where Mebufotenin was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase1
    8
  • phase2
    6
  • Last recorded human test NCT05800860
    2025-03-11

recorded 2026-09-01 · last checked 2026-09-04

Mebufotenin was tested only in human — what did it show?


human: biomarker (12): the rungs where Mebufotenin has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Maximum Plasma Concentration (Cmax) following sublingual administration of 5-MeO-DMT. — the recorded outcome words.

Yeast C. elegans Drosophila Mouse Rat Dog Non-human primate Human biomarker
Show the evidence
  • human NCT06816667
    biomarker; Maximum Plasma Concentration (Cmax) following sublingual administration of 5-MeO-DMT.; 12

recorded 2026-09-01 · last checked 2026-09-04

3 of Mebufotenin's trials stopped: accrual/recruitment, other?


accrual/recruitment (2) and other (1): Mebufotenin's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"Recruitment of this patient population was more challenging than anticipated. The sponsor concluded that a sufficient amount of patients have completed the trial to demonstrate proof of concept in this patient population."; 3 of 12 registered studies

Show the evidence

Trial

  • NCT05804708
    terminated; "Recruitment of this patient population was more challenging than anticipated. The sponsor concluded that a sufficient amount of patients have completed the trial to demonstrate proof of concept in this patient population."
  • NCT05839509
    terminated; "Recruitment of this patient population was more challenging than anticipated. The sponsor concluded that a sufficient amount of patients have completed the trial to demonstrate proof of concept in this patient population."
  • NCT06810765
    withdrawn; "Study is being conducted externally."

recorded 2026-09-01 · last checked 2026-09-04

Could one person measure Mebufotenin's effect on treatment emergent aes?


Treatment emergent aes: measured in Mebufotenin's trials.

Interpretation treatment emergent aes is the recorded endpoint.

Show the evidence

biomarkers

  • treatment emergent aes; 2026-09-01
  • incidence of adverse events; 2026-09-01
  • human trials at or under30
    6
  • Not recorded for this substance
    a recorded half-life
  • smallest human trial
    0; NCT06810765; PHASE2; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN

What will the one ongoing trial of Mebufotenin report, and when?


1 registered trial of Mebufotenin is open; earliest completion 2026-05. ClinicalTrials.gov · 2026-09-01

Interpretation Serum PK parameters of mebufotenin - maximum observed concentration (Cmax)

Show the evidence
  • Trial NCT07540494
    "Pharmacokinetics and Safety of GH001 Delivered Via a GH001 Aerosol Delivery System in Healthy Subjects"; n 12; "Serum PK parameters of mebufotenin - maximum observed concentration (Cmax)"; 2026-05

recorded 2026-09-01 · last checked 2026-09-04

Which 6 trials of Mebufotenin posted no result?


Posted no result
6 of 6 completed trials
Registrations
NCT04640831, NCT04698603, NCT05163691, NCT05032833, NCT05698095 and NCT05753956
Completion dates
oldest 2019-10-04; newest 2023-11-29
Show the evidence

Trial

  • NCT04640831
    2019-10-04
  • NCT04698603
    2021-11-06
  • NCT05163691
    2021-11-22
  • NCT05032833
    2022-07-07
  • NCT05698095
    2023-09-07
  • NCT05753956
    2023-11-29

At the median, Mebufotenin's trials enrolled 29 people — anything larger?


Median enrolment
29
Largest enrolment
81
Registered trials counted
12
Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL7257
PubChem CID
1832
CAS number
1019-45-0
InChIKey
ZSTKHSQDNIGFLM-UHFFFAOYSA-N
Also called
5-meo-dmt, 5-methoxydimethyltryptamine, 5-methoxy-n-dimethyltryptamine, Mebufotenina, Mebufotenine, 5-methoxy-n,n-dimethyltryptamine, gh001, mebufotenin [INN]
Development code
NSC-88624
Trade name
GH001, a vaporised synthetic formulation in clinical development; the INN assigned to the molecule is mebufotenin
Sources (3)

Sources

ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 3 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
  • no raw internal fields: enforced by the copy-contract test over the rendered page

This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.