Cybin Advances DMT Research for Treatment-Resistant Depression

Recent clinical trial data sheds light on the potential of dimethyltryptamine (DMT) fumarate as a novel treatment for moderate-to-severe major depressive disorder (MDD) that has not responded to conventional therapies. The research, sponsored by Cybin UK Ltd (formerly Small Pharma), demonstrates the safety and tolerability of DMT, alongside promising signals of efficacy.

Trial Design and Methodology

The phase IIa, double-blind, placebo-controlled, randomized clinical trial was conducted at Hammersmith Medicines Research (HMR), MAC Clinical Research (MAC), and Imperial College London Hammersmith Campus. The study evaluated the effects of a single or double intravenous (IV) dose of DMT fumarate (SPL026) in participants with MDD who had previously failed to respond to at least two prior treatments – either pharmacological or psychotherapeutic. Cybin acquired Small Pharma Inc. In October 2023.

A total of 34 participants were randomized into the study. The trial followed a two-stage design: Stage 1 involved a single dose of DMT or placebo, while Stage 2 provided a second dose to participants who received placebo in Stage 1 (PA group) or a second DMT dose to those who received DMT initially (AA group). A third group, deemed unsuitable for a second dose, continued to follow-up after their first dose (A- arm). The DMT fumarate was administered at a dose of 21.5 mg via IV infusion over 10 minutes.

Throughout the trial, participants received time-limited, relational psychotherapeutic support focused on psychological flexibility. Data was collected using an electronic case report form (Medrio EDC system) and analyzed by HMR, with oversight from the sponsor.

Key Findings and Outcomes

The primary outcome measure was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at two weeks after the first dose. Secondary measures included MADRS scores at various time points, as well as assessments using the Beck Depression Inventory-II (BDI-II) and the Spielberger State-Trait Anxiety Inventory (STAI-T). Additional subjective measures, such as the Mystical Experience Questionnaire (MEQ), were also employed to assess the acute psychedelic experience.

The trial adhered to International Council for Harmonization Good Clinical Practice guidelines and was approved by the UK Medicines and Healthcare products Regulatory Agency and the London–Brent Research Ethics Committee. All participants provided written informed consent. The trial is registered on ClinicalTrials.gov (NCT04673383) and ISRCTN (ISRCTN63465876).

Safety and Tolerability

The study demonstrated that DMT fumarate was generally safe and well-tolerated in the participant cohort. Adverse events were recorded and categorized by severity and relationship to treatment. Safety monitoring included blood pressure, heart rate, and electrocardiograms (ECGs).

Future Directions

Cybin’s acquisition of Small Pharma has created an international clinical-stage leader in novel psychedelic therapeutics. The combined company’s DMT programs represent the largest dataset of systematic research on these short-duration psychedelic molecules. Cybin continues to investigate the therapeutic potential of DMT for MDD and other mental health conditions.

About Cybin UK Ltd

Cybin UK Ltd, formerly Small Pharma, is a company focused on the development of psychedelic therapeutics. Companies House lists Cybin UK Ltd as a registered company in the United Kingdom.