Mebufotenin (BPL-003, GH001) for Depression: 2026 Evidence

The drug

What mebufotenin is, and the two drugs made from it

Mebufotenin is 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), a short-acting psychedelic. Two companies have tested it for treatment-resistant depression, by two different routes.

BPL-003 is a nasal spray of mebufotenin benzoate. It was developed by Beckley Psytech, part of AtaiBeckley, and is now owned by Eli Lilly, which calls it “its lead investigational program for treatment-resistant depression.”
GH001 is an inhaled form, developed by GH Research.
How it acts. It works on the 5-HT1A and 5-HT2A serotonin receptors. After the nasal spray, its effects peak at 8 to 15 minutes and return to baseline after 45 to 60 minutes, Medical Republic reports, citing the JAMA paper’s background.

Status

Where mebufotenin stands as of November 11, 2026

As of November 11, 2026, ClinicalTrials.gov lists no Phase 3 trial of BPL-003 or GH001, and neither drug is FDA-approved.

Phase 3 work. In its quarterly report filed August 11, 2026, AtaiBeckley told the SEC that BPL-003 Phase 3 activities in treatment-resistant depression were initiated in the second quarter of 2026 (Form 10-Q). No Phase 3 trial is registered on ClinicalTrials.gov yet.
Not approved. AtaiBeckley calls BPL-003 “an investigational product” that “has not been approved by the FDA” (March 3, 2026).
Schedule I. 5-MeO-DMT is a Schedule I controlled substance under federal law (21 CFR 1308.11). The terms of Lilly’s purchase include a payment that depends on “U.S. regulatory approval and DEA rescheduling of BPL-003” (Form 8-K).
BPL-003. FDA Breakthrough Therapy designation in October 2025 (Psychiatric Times). An end-of-Phase 2 meeting with the FDA, announced March 3, 2026. Owned by Eli Lilly since September 11, 2026.
Timing. AtaiBeckley expected Phase 3 results in “early 2029” (May 12, 2026), before the Lilly purchase. Approval is years away.
GH001. The FDA lifted its clinical hold on January 5, 2026, and in July 2026 said GH001’s manufacturing and device plans “appear Phase 3 ready” (GH Research).

The full dated timeline is further down this page.

Plain English

Words you will see in these trials

MADRS. A depression rating scale scored from 0 to 60. Higher means more severe.
Response. The MADRS score fell by at least half.
Remission. The MADRS score fell to 10 or less: few symptoms left.
Placebo. A look-alike with no active drug, so results can be compared fairly.
Low-dose comparison. A very small dose of the same drug, used instead of a placebo. BPL-003’s trial used 0.3 mg.
Adverse event. Any health problem reported after dosing, whether or not the drug caused it.
Open-label. Everyone knows what they were given, and there is no comparison group.

Side by side

BPL-003 and GH001 compared

The two programs used different routes, comparison groups and time points, so their headline numbers cannot be compared directly.

BPL-003 and GH001: route, trial, comparison, result, owner and status, November 11, 2026
Question	BPL-003 (nasal spray)	GH001 (inhaled)	Sources
How it is given	Nasal spray of mebufotenin benzoate: one spray into one nostril, given by a trained clinician	Inhaled, as up to 3 increasing doses (6 mg, 12 mg, 18 mg) in a single day	BPL-003 · GH001
Who develops it now	Eli Lilly, since it completed its purchase of AtaiBeckley on September 11, 2026	GH Research	BPL-003 · GH001
Main trial so far	Phase 2b, 193 people analysed at 38 sites in Australia, Europe and the US (NCT05870540)	Phase 2b, 81 people enrolled at sites in Europe: Czechia, Germany, Ireland, the Netherlands, Poland and Spain (NCT05800860)	BPL-003 · GH001
Compared with	A low 0.3 mg dose of the same drug, not a placebo	A placebo	BPL-003 · GH001
Headline result	Day 29: 34.8% (8 mg) and 34.2% (12 mg) responded, against 12.2%; 26% and 18% in remission, against 8%	Day 8: 57.5% in remission, against 0% with placebo	BPL-003 · GH001
Ready to go home	Within 2 hours for 85% (8 mg) and 78% (12 mg); the protocol still required a 4-hour stay	Within 1 hour for 99% (company-reported)	BPL-003 · GH001
Published in a journal?	Yes: JAMA, October 26, 2026	Yes: JAMA Psychiatry, March 25, 2026	BPL-003 · GH001
FDA status	Not approved. Breakthrough Therapy designation, October 2025	Not approved. FDA clinical hold lifted January 5, 2026	BPL-003 · GH001
Phase 3	Phase 3 activities initiated in the second quarter of 2026 (AtaiBeckley 10-Q, August 2026); results expected early 2029 (May 2026). None listed on ClinicalTrials.gov	Targeted to start in 2026 (GH Research, August 2026). None listed on ClinicalTrials.gov	BPL-003 · GH001 · GH001

Different designs, comparison groups and time points: this is not a head-to-head comparison. Each row links its BPL-003 and GH001 sources, all read November 11, 2026. GH001 figures are as reported by GH Research.

The JAMA trial

BPL-003: one nasal spray, tested in 193 people

A single spray of BPL-003 beat a low 0.3 mg dose on response and remission at day 29, and the gap was still there at day 57.

A long, empty hospital corridor with cream walls, a red stripe, and ceiling lights — In the BPL-003 trial, a trained clinician gave each spray and people stayed under observation for at least 4 hours. Photo: a hospital corridor, not from the trial; W.carter, released under CC0 (public domain), via Wikimedia Commons.

Who took part. The trial, published in JAMA on October 26, 2026 (PubMed record), randomized 196 people and analysed 193.

Adults aged 18 to 75 with moderate to severe major depression.
Not helped by 2 to 5 antidepressant trials in the current episode.
Average age 41; 59.1% women.
38 sites in Australia, Germany, Poland, Spain, the UK and the US (Medical Republic).
On average 13.4 years with depression and 2.3 antidepressants that had not worked.

How it was run. A Phase 2b, randomized, double-blind trial (NCT05870540), funded by Beckley Psytech, an AtaiBeckley company.

People stopped their antidepressants under supervision before dosing. The drug was given alone.
Each person got one dose: 8 mg (46 people), 12 mg (73) or 0.3 mg (74). The 0.3 mg dose was the comparison, not a placebo.
A trained clinician gave one spray into one nostril.
Everyone stayed more than 4 hours afterwards, with psychological support.

BPL-003 Phase 2b trial: response, remission, side effects and MADRS change by dose, with sources
Result	8 mg	12 mg	0.3 mg (comparison)	Source
Responded at day 29	34.8%	34.2%	12.2%	HMP
In remission at day 29	26%	18%	8%	JAMA
Responded at day 57	28.3%	31.5%	10.8%	Medical Republic
In remission at day 57	26.1%	19.3%	8.1%	Medical Republic
Had any adverse event	76.1%	84.9%	73.0%	HMP
Average drop on the MADRS by day 29 (difference from 0.3 mg)	12.5 points (6.2 more; P = .003)	11.1 points (5.3 more; P = .003)	5.5 points	JAMA

Day 29 response is HMP’s figure; the JAMA summary rounds it to 35%, 34% and 12%. Both active doses did better than 0.3 mg from day 2 through day 57, HMP reports.

Ready to go home in about 2 hours, kept for 4. Within 2 hours, 85% of the 8 mg group and 78% of the 12 mg group were judged ready for discharge (HMP). The average was 113.7 minutes with 8 mg, 117.3 with 12 mg and 106.2 with 0.3 mg (Medical Republic). The protocol required a 4-hour stay, so no one actually left before 4 hours.

Side effects. Almost all adverse events were mild or moderate.

99.7% of adverse events were mild or moderate (HMP).
Most common across all participants: headache (29.5%), nausea (23.8%) and pain where the spray went in (15.5%) (Medical Republic).
One person on 12 mg had two severe panic attacks, judged to be caused by the treatment (HMP).
No suicidal behaviour was recorded. Suicidal thoughts reported in the active groups came without intent, and only in people with a history of them (Medical Republic).

Company figures

A second dose: open-label results with no comparison group

These figures come from the company, were not published in a journal, and had no comparison group.

107 of 126 eligible people took a second 12 mg dose, 8 weeks after the first (AtaiBeckley, November 10, 2025).
Of the 60 who had an active dose first, 63% were responding and 48% were in remission 8 weeks after the second dose (week 16).
One serious drug-related adverse event came 8 days after the second dose. It resolved with in-patient monitoring.

The inhaled version

GH001: tested against a placebo

In GH001’s Phase 2b trial, 57.5% of people were in remission at day 8, against 0% with placebo, according to GH Research.

The trial. NCT05800860 enrolled 81 people with treatment-resistant depression. ClinicalTrials.gov lists it as completed and quadruple-masked: participants and staff were not told who got what.
Published. In JAMA Psychiatry on March 25, 2026 (GH Research).
Six months, open-label. 73% were in remission at 6 months in the open-label extension, after about 4 treatments on average. There was no comparison group (GH Research).
Short sessions. GH Research reports a median psychoactive experience of about 11 minutes, 99% ready for discharge within 1 hour, and no treatment-related serious adverse events.
U.S. status. The FDA had put GH001’s U.S. application on clinical hold, which stops trials under it. It lifted the hold on January 5, 2026. In July 2026 the FDA said GH001’s manufacturing and device plans “appear Phase 3 ready,” and GH Research is aiming to start its pivotal program in 2026 (August 6, 2026).

Read with care

What the JAMA editorial and the authors warn about

An editorial in the same issue of JAMA found the results notable, but said “the antidepressant effect was incomplete,” as quoted by the Hindustan Times.

The editorial, by Chittaranjan Andrade, praised the 8-week effect of a single dose and how soon people were ready to leave. It also raised these points, as PsyPost summarises them:

The average participant improved by only about 30%.
Response and remission rates fell below those typically seen with ketamine and ECT.
Higher or rising doses, or a course of treatments, may be worth testing.
Participants were not markedly treatment-resistant: the median was two antidepressants that had not worked.
The trial could not test the effect on suicidal thinking.

The trial’s own limitations, from the JAMA summary and PsyPost:

Most participants and on-site clinicians correctly guessed which group they were in.
The 8 mg group was smaller, after a change to how people were randomized.
Everyone had to stop antidepressants first, so results may not apply to people who cannot.
Nearly 90% of participants were white.
The psychological support was not tested on its own.
Employees of the sponsor helped design the trial, analyse it and decide to publish.

Who the results do not cover

People the BPL-003 trial left out

If any of these apply to you, the trial results say nothing about how you would respond.

PTSD, bipolar disorder or a psychotic disorder.
Any personality disorder.
A parent, sibling or child with schizophrenia or bipolar disorder.
Suicidal thoughts with intent in the past year.
Ketamine or ECT that did not work before. Many people reading about treatment-resistant depression have tried one of these.
Anyone younger than 18 or older than 75, or unable to stop their antidepressants.

Exclusions as reported by PsyPost; age range and antidepressant washout from the JAMA summary and Medical Republic.

A psychiatrist’s view

Dr. Savatta: impressive, if it holds up

Dr. Salvatore G. Savatta, a psychiatrist and this site’s Clinical Review Lead, set out his view in an email on November 11, 2026, when he asked for this page:

More treatments are still needed. Every existing treatment has people it does not help, and some people cannot have some treatments for medical reasons.
The single-dose response rates are very impressive, if they hold up in larger placebo-controlled studies.

The “if” matters. BPL-003 was compared with a low 0.3 mg dose, not a placebo. Its Phase 3 trials would compare it with a placebo. AtaiBeckley says that work began in the second quarter of 2026, but no Phase 3 trial is listed yet.

Why more options matter. In the BPL-003 trial itself, about 65% of the 8 mg group had not responded by day 29. And some current treatments are ruled out for some people:

The FDA label rules SPRAVATO out for people with an aneurysm or aneurysmal blood vessel disease, an arteriovenous malformation, a past bleed inside the brain, or an allergy to esketamine or ketamine (Labyrinth Psychiatry Group).
TMS is generally not used for people with metal or electronic devices in or near the head, such as deep brain stimulators, cochlear implants or aneurysm clips (Labyrinth Psychiatry Group).

Dr. Savatta is affiliated with Labyrinth Psychiatry Group. His view is taken from his email; his review of this page is pending.

The timeline

Where approval stands, date by date

The latest milestone is the JAMA paper of October 26, 2026. No Phase 3 trial is listed yet, and there is no FDA decision date.

BPL-003 and GH001: dated events and sources, read November 11, 2026
Date	What happened	Source
October 2025	The FDA grants BPL-003 Breakthrough Therapy designation for treatment-resistant depression. It is not an approval.	Psychiatric Times
November 10, 2025	AtaiBeckley reports company topline results after a second, open-label dose of BPL-003.	AtaiBeckley
January 5, 2026	The FDA lifts the clinical hold it had placed on GH001's U.S. application.	GH Research
March 3, 2026	After an end-of-Phase 2 meeting, AtaiBeckley says the FDA “indicated support” for Phase 3 trials of BPL-003.	AtaiBeckley
March 25, 2026	GH001's placebo-controlled Phase 2b trial is published in JAMA Psychiatry.	GH Research
May 12, 2026	AtaiBeckley says Phase 3 will start in the second quarter of 2026, with topline results expected in “early 2029.”	SEC
July 2026	The FDA tells GH Research that GH001's manufacturing and device plans “appear Phase 3 ready.”	GH Research
August 11, 2026	In its quarterly report to the SEC, AtaiBeckley says BPL-003 Phase 3 activities in treatment-resistant depression were initiated in the second quarter of 2026.	SEC
September 11, 2026	Eli Lilly completes its purchase of AtaiBeckley. BPL-003 is now a Lilly program; Lilly's release gives no Phase 3 start date.	Lilly
October 26, 2026	JAMA publishes the BPL-003 Phase 2b trial, with an editorial in the same issue.	JAMA
November 11, 2026	ClinicalTrials.gov lists no Phase 3 trial of BPL-003 or GH001.	ClinicalTrials.gov
Not set	An FDA decision on either drug. No date exists: Phase 3 results for BPL-003 were expected in early 2029.	SEC

What BPL-003’s Phase 3 would look like. AtaiBeckley described two trials after its March 2026 FDA meeting:

ReConnection-1: about 350 people, one dose of 8 mg, 4 mg or placebo.
ReConnection-2: two doses, on day 1 and day 15, of 8 mg or placebo.
Both: 12 weeks with a placebo group, then a 52-week open-label extension. The main measure is the change in MADRS score at week 4.

A realistic timeline. By AtaiBeckley’s own estimate in May 2026, before the Lilly purchase, Phase 3 results would come in early 2029. That puts any approval not before 2029 at the earliest, by the company’s own timeline. In its August 11, 2026 quarterly report, AtaiBeckley told the SEC that Phase 3 activities had been initiated in the second quarter of 2026. Lilly has not given a Phase 3 start date.

What ClinicalTrials.gov shows. Searches on November 11, 2026 for BPL-003, GH001, mebufotenin and 5-MeO-DMT found no Phase 3 trial of either drug. The BPL-003 records are the completed JAMA trial (NCT05870540), an open-label Phase 2 study listed as recruiting (NCT05660642), a Phase 1 study (NCT05347849) and a Phase 2 study in alcohol use disorder (NCT05674929).

Do not self-treat

Toad secretion and retreats are not the medicine in these trials

The trials used measured doses, screened people first and watched them for hours. Retreat use does none of that.

A large gray-green toad with an amber eye and a pale wart near its mouth, sitting on a rock — The Sonoran Desert toad, the only animal known to secrete 5-MeO-DMT (PLOS One, 2025). Photo: Saguaro National Park, National Park Service (public domain), via Wikimedia Commons.

5-MeO-DMT occurs in some plants and in the secretion of at least one toad species (Medical Republic).
Outside trials, people smoke dried toad secretion at retreats without medical screening, the Hindustan Times reported on October 31, 2026.
That is not BPL-003 or GH001, and the trial results do not apply to it. 5-MeO-DMT is a Schedule I controlled substance under federal law (21 CFR 1308.11).

Your options today

If you have treatment-resistant depression now

Mebufotenin is years away from any FDA decision. These pages on this site cover the options to discuss with a psychiatrist now.

Treatment-resistant depressionWhat the term means, reassessment, and the options a psychiatrist may discuss Medication strategiesOptimizing, switching, combining and augmenting antidepressants TMS for depressionWhat TMS involves and what to ask before starting SPRAVATO (esketamine)Side effects and safety rules for the supervised esketamine nasal spray KetamineOff-label and compounded ketamine pathways Ketamine therapy costWhat infusions cost and what insurance covers ECT for depressionWhat ECT involves and what to expect TMS, SPRAVATO and ketamine comparedSide effects and cost side by side ECT vs TMSHow the two treatments compare COMP360 psilocybinA different psychedelic, further along: where its FDA application stands

In New Jersey. Labyrinth Psychiatry Group explains what the trial means for New Jersey patients, including what 5-MeO-DMT’s legal status means there.

If you hope to join a trial. Read each study’s rules on ClinicalTrials.gov with your psychiatrist before you change treatment. The BPL-003 trial required people to stop antidepressants first, and it excluded anyone whose ketamine or ECT had not worked.

Printable

Questions for your psychiatrist about mebufotenin

Write the answers down. Keep health details for the visit, not for a web form.

Does my history fit treatment-resistant depression, and what have I not tried yet?
Would anything in my history have kept me out of the BPL-003 trial (PTSD, bipolar disorder, psychosis, a personality disorder, a family history of schizophrenia or bipolar disorder, or ketamine or ECT that did not work)?
Is any treatment I am considering ruled out for me for a medical reason?
Which option fits me now, and would starting it affect joining a trial later?
Is there a study I could qualify for, and would I have to stop my antidepressant first?
What should I do if my depression gets worse while I wait?

Common questions

Mebufotenin, BPL-003 and GH001: questions people ask

What is mebufotenin?

Mebufotenin is another name for 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), a short-acting psychedelic. Two drugs based on it are being studied for treatment-resistant depression: BPL-003, a nasal spray of mebufotenin benzoate, and GH001, which is inhaled.

Is mebufotenin a psychedelic?

Yes. Mebufotenin (5-MeO-DMT) is a short-acting psychedelic. With the BPL-003 nasal spray, most people in the JAMA trial were judged ready to leave the clinic within 2 hours (85% on 8 mg, 78% on 12 mg), although the study kept everyone at least 4 hours. GH Research reports a median experience of about 11 minutes with inhaled GH001.

Is mebufotenin FDA approved?

No. AtaiBeckley calls BPL-003 “an investigational product” that “has not been approved by the FDA.” GH001 is still preparing for Phase 3. As of November 11, 2026, ClinicalTrials.gov lists no Phase 3 trial of BPL-003 or GH001.

What phase is BPL-003 in?

BPL-003 has finished a Phase 2b trial, published in JAMA on October 26, 2026. In March 2026 the FDA indicated support for Phase 3, in May 2026 AtaiBeckley said Phase 3 would start in the second quarter of 2026, with results expected in early 2029, and in its August 11, 2026 quarterly report it told the SEC that Phase 3 activities had been initiated in that quarter. As of November 11, 2026, no Phase 3 trial of BPL-003 is listed on ClinicalTrials.gov.

Who owns BPL-003?

Eli Lilly. Lilly completed its purchase of AtaiBeckley on September 11, 2026, and calls BPL-003 “its lead investigational program for treatment-resistant depression.” Lilly's release gives no Phase 3 start date.

How well did the BPL-003 nasal spray work?

At day 29, 34.8% of people given 8 mg and 34.2% given 12 mg had responded, against 12.2% given a low 0.3 mg dose. In remission: 26% and 18%, against 8%. The comparison was a low dose of the same drug, not a placebo, and an editorial in JAMA noted that the average participant improved by only about 30%.

What is the difference between BPL-003 and GH001?

Both are mebufotenin. BPL-003 is a nasal spray of mebufotenin benzoate, now owned by Eli Lilly, and was compared with a low 0.3 mg dose in its Phase 2b trial. GH001 is inhaled, made by GH Research, and was compared with a placebo. The trials used different designs and time points, so their results cannot be compared head to head.

What did the GH001 trial find?

GH001 was compared with a placebo. At day 8, 57.5% of people given GH001 were in remission, against 0% given placebo, according to GH Research. The results were published in JAMA Psychiatry in March 2026.

Is mebufotenin (5-MeO-DMT) legal?

Mebufotenin is 5-MeO-DMT, a Schedule I controlled substance under federal law (21 CFR 1308.11, read November 11, 2026). The terms of Lilly's purchase of AtaiBeckley include a payment that depends on “U.S. regulatory approval and DEA rescheduling of BPL-003.” Toad secretion used at retreats is not the drug tested in these trials.

Can I get mebufotenin for depression now?

No mebufotenin product is FDA-approved, so outside a research study there is no approved way to receive it. Advanced Depression Care is an education site and does not treat patients. This page is not an offer of mebufotenin from Labyrinth Psychiatry Group or any clinic.

Sources

Where every figure on this page comes from

Every source was read November 11, 2026. Company figures are labelled as company figures. Trial numbers are group results and do not predict any one person’s response. This page does not recommend mebufotenin or any other treatment for a particular person.