Psychedelic · BPL-003
BPL-003 (intranasal 5-MeO-DMT benzoate)
- Breakthrough Therapy
Patent-protected intranasal benzoate salt of 5-MeO-DMT (mebufotenin), a short-acting serotonergic psychedelic nasal spray designed for rapid, durable single-dose antidepressant effects within a ~2 hour treatment window. Lead indication treatment-resistant depression; also studied in alcohol use disorder.
Also known as: BPL-003, mebufotenin benzoate, 5-MeO-DMT
- Modality
- Psychedelic
- Chemical class
- tryptamine
- DEA schedule
- Schedule I
- Chemistry
- Achiral
- Mechanism
- 5-HT1A agonist
- Highest phase
- Phase 2
- Lead indication
- Treatment-resistant depression
- Developer
- Beckley Psytech Limited (ATAI)
- Designations
- Breakthrough Therapy
- Trials
- 3 tracked · 1 recruiting · 47 sites
Mechanism of action
Delivers 5-MeO-DMT, a non-selective serotonergic agonist with highest affinity at 5-HT1A and additional 5-HT2A activation; 5-HT2A agonism mediates classic psychedelic effects while potent 5-HT1A agonism shapes its short-acting profile.
| Target | Action | Affinity |
|---|---|---|
| 5-HT1AprimaryHTR1A | Agonist | Ki 1.9 nMⓘ |
| 5-HT2AHTR2A | Agonist | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| BPL-003 intranasal dry powderAptar Unidose dry-powder intranasal spray device Single intranasal dose; doses of 8 mg and 12 mg studied in Phase 2b TRD (8 mg selected for Phase 3); 1-12 mg range in Phase 1 SAD. | Intranasal | Single dose | t½ 0.33 h · Tmax 0.15 h |
Development timeline
- FDA granted Breakthrough Therapy Designation for BPL-003 in TRD; Phase 3 planned ~Q2 2026.Treatment-resistant depression↗
- Positive Phase 2b topline: single 8 mg / 12 mg dose produced rapid significant MADRS reductions vs 0.3 mg comparator at Day 29, largely maintained to Day 57.Treatment-resistant depression↗
- metBPL-003 Phase 2a open-label AUD study positive topline: single 10 mg dose + psychological support cut heavy drinking days (56%->13%) and raised abstinent days (33%->81%) at Week 12, with 50% maintaining complete abstinence over 3 months; well tolerated, no serious/severe AEs.Alcohol use disorder↗
BPL-003 (intranasal 5-MeO-DMT benzoate) for Treatment-resistant depression
Phase 2ActiveTreatment-resistant depression indication →
BPL-003 (intranasal mebufotenin) for treatment-resistant depression. Phase 2b (NCT05870540, n=196) met its primary endpoint with rapid, durable single-dose MADRS reductions (8 mg -12.1, 12 mg ~-10.8 to -11.1 vs 0.3 mg -5.8 at Day 29). FDA Breakthrough Therapy granted Oct 2025; pivotal Phase 3 planned ~Q2 2026. Also in development for alcohol use disorder.
BPL-003 (intranasal 5-MeO-DMT benzoate) for Alcohol use disorder
Phase 2CompletedAlcohol use disorder indication →
BPL-003 (intranasal mebufotenin / 5-MeO-DMT benzoate) for moderate-to-severe alcohol use disorder. A single 10 mg intranasal dose combined with relapse-prevention psychological support was evaluated in an open-label Phase 2a study (NCT05674929, King's College Hospital, London; 13 enrolled, 12 analyzed). Positive topline reported 2025-01-28: 50% of patients (6/12) maintained complete abstinence over 3 months, mean heavy drinking days fell from 56% to 13% and abstinent days rose from 33% to 81% at Week 12, with no serious or severe adverse events and most patients discharge-ready within ~2 hours. Secondary (non-lead) indication; lead indication is treatment-resistant depression.
Readouts
- 2025-01-28ReportedTopline datametNCT05674929
BPL-003 Phase 2a open-label AUD study positive topline: single 10 mg dose + psychological support cut heavy drinking days (56%->13%) and raised abstinent days (33%->81%) at Week 12, with 50% maintaining complete abstinence over 3 months; well tolerated, no serious/severe AEs. ↗
Clinical trials
NCT05870540Phase 2Completedn=196
Dose-Finding Study of Intranasal BPL-003 in Treatment-Resistant Depression (with OLE)
metprimaryMADRS change at Day 29 — 8 mg -12.1; 12 mg ~-10.8 to -11.1; vs 0.3 mg -5.8
Single dose; 8 mg and 12 mg statistically significant vs comparator, effects largely maintained to Day 57 (company PR / press coverage).
NCT05674929Phase 2Completedn=13
An Open-Label, Phase 2a Single Dose Study in Patients With Alcohol Use Disorder
metsecondaryComplete abstinence maintained over 3-month follow-up — 6 of 12 patients (50%) maintained complete abstinence over 3 months
Open-label single 10 mg dose of BPL-003 with relapse-prevention psychological support; 50% of analyzed patients maintained complete abstinence across the 3-month observation period (company topline).
metsecondaryMean percentage of heavy drinking days at Week 12 — 56% (pre-dose) -> 13% (Week 12)
Mean percentage of heavy drinking days declined from 56% in the pre-dose period to 13% at Week 12 after a single dose plus psychological support (open-label, n=12 analyzed).
metsecondaryMean percentage of abstinent days at Week 12 — 33% (pre-dose) -> 81% (Week 12); mean alcohol units/day 9.3 -> 2.2
Mean percentage of abstinent days rose from 33% pre-dose to 81% at Week 12 and mean alcohol units/day fell from 9.3 to 2.2; BPL-003 was well tolerated with only mild/moderate AEs, no serious or severe adverse events, and most patients discharge-ready within ~2 hours (open-label, n=12 analyzed).
NCT05660642Phase 1/2Recruitingn=64
Open-Label Phase 2a Study of BPL-003 in Treatment Resistant Depression
Identifiers
- ChEMBL CHEMBL7257
- PubChem CID 1832
- FDA UNII X0MKX3GWU9
Sources
- An Open-Label, Phase 2a Single Dose Study in Patients With Alcohol Use Disorder (NCT05674929) — ClinicalTrials.gov
- atai Life Sciences Announces Positive Topline Results from Beckley Psytech's BPL-003 Phase 2a Open-Label Study for Alcohol Use Disorder — atai Life Sciences / Beckley Psytech
- BPL-003 Phase 2b (NCT05870540) — ClinicalTrials.gov
- BPL-003 Phase 2b results — Psychedelic Alpha
- FDA Breakthrough Therapy for BPL-003 — atai / Beckley Psytech
- clinicaltrials.gov — ClinicalTrials.gov
- en.wikipedia.org — Reference
- 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-MeO-DMT benzoate) in healthy participants — Journal of Psychopharmacology (PMC)