Publication of Phase 1 Results Announced for BPL-003

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Phase 1 results of BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate)—a short-duration psychedelic tryptamine that binds to multiple serotonergic receptors—have been published in The Journal of Psychopharmacology.¹

The phase 1 double-blind, placebo-controlled study, which involved a single ascending dose, examined the safety, tolerability, pharmacokinetics, and pharmacodynamics of BPL-003 in 44 psychedelic-naïve healthy volunteers. Participants were divided into 7 cohorts and administered either a single dose of BPL-003 ranging from 1 mg to 12 mg or a placebo.¹

The study results showed that the participants tolerated BPL-003 well, even at doses up to 12 mg. There were no reports of serious adverse events. The majority of reported adverse events were mild, with common ones including nasal discomfort, nausea, headache, and vomiting. 5-MeO-DMT was swiftly absorbed and cleared from the body, reaching peak plasma concentration in about 8 to 10 minutes and exhibiting a mean terminal elimination half-life of less than 27 minutes.²

Systemic exposure to 5-MeO-DMT increased proportionally with the dose, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine remained negligible. Subjective drug intensity ratings were linked to plasma 5-MeO-DMT concentrations.²

Additionally, scores on the Mystical Experience Questionnaire (MEQ-30) and Ego Dissolution Inventory (EDI) generally rose with increasing BPL-003 doses, with 60% of participants reporting a “complete mystical experience” at doses of 10 and 12 mg. Notably, BPL-003 induced profound and emotionally intense alterations in consciousness, characterized by rapid onset and short duration.²

These results suggest the potential for a scalable, single-dose treatment approach that aligns with current intervention strategies. “The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in pharmacokinetic and pharmacodynamic effects,” the investigators concluded. “The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials.”²

“We are pleased by the publication of the BPL-003 phase 1 data in The Journal of Psychopharmacology, a well-regarded, peer-reviewed journal,” said Florian Brand, CEO and co-founder of BPL-003 investor atai Life Sciences, in a press release.

“Consistent with the initial phase 2a data reported recently, the phase 1 results showed that BPL-003 was safe and well-tolerated and underscore its potential as a scalable interventional treatment requiring 2 hours or less in the clinic, in line with the treatment paradigm successfully established by Spravato®.”¹

In March 2024, atai Life Sciences reported positive initial results from its phase 2a open-label study of BPL-003 for TRD (NCT05660642). The results showed that a single 10-mg dose of the treatment led to rapid, durable reduction of symptoms of depression in patients with TRD.³

“The positive data from the phase 2a study is highly encouraging as we await the results of the larger phase 2b study anticipated later this year,” Brand said upon announcement of the phase 2a results. “With around half of TRD patients in remission 3 months after just a single dose of BPL-003 in this study, we are particularly excited about its antidepressant durability potential.”³

BPL-003 is also currently undergoing phase 2a studies for alcohol use disorder (NCT05674929) and is being investigated in a multi-site phase 2b study for TRD (NCT05870540), with initial results anticipated in the second half of 2024.1 The development of BPL-003 and fellow short-duration psychedelic candidate ELE-101 is part of a strategic investigation and collaboration between atai Life Sciences and Beckley Psytech.⁴

Read the full phase 1 study in The Journal of Psychopharmacology here.

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of treatment-resistant depression, alcohol use disorder, and a wide variety of other psychiatric disorders at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.

References

1. atai Life Sciences announces the publication of Beckley Psytech’s phase 1 study of BPL-003 in the Journal of Psychopharmacology. atai Life Sciences. News release. April 17, 2024. Accessed April 17, 2024. https://ir.atai.life/news-releases/news-release-details/atai-life-sciences-announces-publication-beckley-psytechs-phase

2. Rucker JJ, Roberts C, Seynaeve M, 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. J Psychopharmacol. 2024;0(0).

3. Kuntz L. BPL-003: rapid, durable treatment for TRD sees positive phase 2 results. Psychiatric Times. March 27, 2024. Accessed April 17, 2024. https://www.psychiatrictimes.com/view/bpl-003-rapid-durable-treatment-for-trd-sees-positive-phase-2-results

4. atai Life Sciences announces strategic investment in Beckley Psytech to accelerate the clinical development of short-duration psychedelics. atai Life Sciences. News release. January 4, 2024. Accessed April 17, 2024. https://ir.atai.life/news-releases/news-release-details/atai-life-sciences-announces-strategic-investment-beckley