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Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial.

Ellen James, David Erritzøe, Tiffanie Benway, Zelah Joel, Christopher Timmermann, Meghan Good, Claudio Agnorelli, Brandon M Weiss, Tommaso Barba, Graham Campbell, Michelle Baker-Jones, Charlotte Hughes, Helen Topping, Malcolm Boyce, Carol Routledge

Frontiers in Psychiatry 2023 DOI: 10.3389/fpsyt.2023.1305796 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial Peer reviewed
Sample size 32
Population Psychedelic-naïve healthy participants
Intervention SPL026 (DMT fumarate)
Dose 9, 12, 17, and 21.5 mg intravenously
Duration Single dose, with follow-up to day 90
Topics Depression DMT 5-MeO-DMT
Keywords Pharmacodynamic Safety Tolerability Psychedelics hallucinogens Entheogens Mental health psychiatry Medical research
Citations 16
Registration NCT04673383
Key findings A 21.5 mg intravenous dose of SPL026 (DMT) was selected as safe and tolerable for use in a subsequent trial in patients with major depressive disorder.

Abstract

Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD). The aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the trial (Part B: not presented in this manuscript). In the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger's state-trait anxiety inventory. SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores. These trends are likely to require confirmation in a larger sample size. Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience. Based on the data obtained from this part of the trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876.

Comparable studies

Other randomized controlled trials on DMT for depression, most cited first.

Study Year Design Participants
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. Healthy psychedelic-naïve participants 2024 Double-blind, placebo-controlled single ascending dose study n = 44
Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study. Adults with moderate to high levels of anxiety and/or depression, without formal... 2025 Randomized controlled trial

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Depression DMT 5-MeO-DMT Anxiety Ego dissolution Mystical experience Mysticism Psychedelic-assisted therapy Serotonin

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DMT for depression