First Participant Dosed in Phase 1b Trial of VLS-01 for TRD


This trial aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of VLS-01 compared with intravenous DMT for treatment-resistant depression.

James Thew_AdobeStock

James Thew_AdobeStock

atai Life Sciences announced that the phase 1b trial of VLS-01, an oral transmucosal film (OTF) formulation of N,N-dimethyltryptamine (DMT), has initiated dosing with the first healthy participant.

This single-center, open-label study aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of VLS-01 compared with intravenous (IV) DMT for treatment-resistant depression (TRD), with plans to enroll a total of 16 healthy participants. Each participant will receive a single dose of IV DMT followed by 3 different doses of VLS-01, with a 28-day washout period between administrations.1

“I am delighted with the swift progress our team has made to commence dosing in the phase 1b trial,” said Florian Brand, atai co-founder and chief executive officer, in a news release. “Our proprietary oral transmucosal formulation of DMT, VLS-01, is designed to induce a short psychedelic effect to allow for scalability and broad patient access. VLS-01 is expected to fit into an established interventional psychiatry treatment paradigm of 2 hours in the clinic and is anticipated to offer a more patient and physician-friendly experience compared to intravenous administration.”

VLS-01 is being developed to address TRD in patients. Pharmacologically, DMT acts as a partial agonist on the 5-HT 1A/2A/2C receptors, characterized by its short duration of psychedelic effect. Clinical studies have shown that a single IV administration of DMT yields rapid and sustained antidepressant effects in individuals with major depressive disorder. atai’s OTF formulation aims to obviate the need for IV administration, enhance pharmacokinetics compared with this route, and maximize therapeutic potential within a 2-hour, in-clinic patient visit.1

This formulation of VLS-01 has undergone optimization based on the results from atai’s previous phase 1 single ascending dose trial, which were announced in October 2023.1,2 The optimization of the formulation included taste masking, the addition of a backing layer, and enhancements to increase permeability. The current optimized formulation is intended to improve pharmacokinetics and patient experience in preparation for an anticipated phase 2 trial with VLS-01 in TRD.1

Identifying effective new treatments for TRD is very important, given the prevalence of TRD. According to Psychiatric Times®, “Estimates indicate as many as 30% of your patients will experience TRD, and that number may change as the definition of TRD is explored, challenged, and honed. As our understanding of depression deepens, so does the complexity of addressing cases that defy conventional therapeutic approaches—and ensuring that patients are receiving the correct diagnosis and a full complement of appropriate treatment. Thus, the landscape of TRD presents an evolving challenge for psychiatric clinicians.”3

Top-line results from atai’s phase 1b trial of VLS-01 are anticipated in the second half of the year.1

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at

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


1. atai Life Sciences announces first participant dosed in phase 1b trial of VLS-01. atai Life Sciences. News release. March 4, 2024. Accessed March 5, 2024.

2. atai Life Sciences announces completion of phase 1 study of VLS-01 in healthy participants. atai Life Sciences. News release. October 2, 2023. Accessed March 5, 2024.

3. Hennessy Jr M. Tackling treatment-resistant depression. Psychiatric Times. November 8, 2023. Accessed March 5, 2024.

Related Videos
brain depression
depression obesity
summer sadness
Experts on MDD.
Experts on MDD.
© 2024 MJH Life Sciences

All rights reserved.