Helus Pharma’s psychedelic compound, SPL026, has demonstrated its potential to treat major depressive disorder (MDD) in a mid-stage study.
During a Phase IIa trial (NCT04673383), 34 patients with moderate-to-severe MDD were randomised to receive either a 21.5mg intravenous dose of SPL026, which contains dimethyltryptamine (DMT), or placebo. All patients involved in this trial had received at least two unsuccessful rounds of treatment, which could include pharmaceutical and/or psychotherapy-based regimens.
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One week after dosing, patients who received SPL026 experienced a significant 10.8-point drop in average Montgomery–Åsberg Depression Rating Scale (MADRS) scores compared with placebo. The MADRS scoring system is a common metric used to measure depression severity in MDD trials.
SPL026’s antidepressant impact was also sustained at the two-week mark, with those given the drug demonstrating an average 7.4-point reduction in MADRS from baseline at this time point.
SPL026 also reduced depression in some patients at both the three- and six-month mark post-treatment, say the Imperial College London-based researchers leading the trial.
The second portion of the trial, in which both the placebo and treatment group received SPL026, also revealed that two doses of the drug offered no significant benefit over a single dose, suggesting that the drug could be effectively administered as a single dose in MDD.
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By GlobalDataThe psychedelic was also proven to be safe and tolerable, with no serious treatment-emergent adverse events (TEAEs) or concerning changes in suicidal thoughts recorded within the study period.
DMT is a naturally occurring psychedelic, which is the major psychoactive compound in ayahuasca. The drug experience lasts approximately 25 minutes, which is significantly shorter than other psychedelics in clinical trials.
Creating ‘no trip’ psychedelics
While synthetic psychedelic molecules have shown promise in clinical trials thus far, researchers on Helus’ trial noted that the drug’s efficacy “appears to be dependent on the intensity of the acute psychedelic experience it generates”. This means that patients experiencing higher intensity ‘trip’-like symptoms may benefit more from treatment.
According to experts previously interviewed by Pharmaceutical Technology, sister publication of Clinical Trials Arena, the hallucinogenic aspect of psychedelics is often unfavourable in the clinical setting for both patients and clinicians. This is because they must be administered in a controlled environment, and patients may not want to have the ‘trip’ when taking such a substance.
The psychoactive component of such therapies also presents a hurdle for trial operators, who must design their trials with functional unblinding in mind.
This has led to the development of non-psychoactive psychedelics, which investigators hope will demonstrate the same therapeutic benefits without provoking a hallucinogenic response. Currently, Delix Therapeutics is looking to advance its home-administered, nonhallucinogenic neuroplastogen, zalsupindole (DLX-001), to Phase II trials in MDD.
Psychedelics garner industry interest
Across the wider pharmaceutical sector, there has been a notable uptick in interest around psychedelics, which are primarily being explored as treatments for mental health conditions like depression, anxiety and post-traumatic stress disorder (PTSD).
Helus, previously known as Cybin, is one of several companies currently looking to commercialise a psychedelic molecule in the mental health arena.
Another is biotech AtaiBeckley, which is planning to initiate a Phase III trial on its mebufotenin benzoate nasal spray for treatment-resistant depression (TRD) in Q2 2026. This follows the positive results of a Phase IIa study (NCT05660642), where two doses of BPL-003 decreased MADRS scores by 19.0 from baseline.
Compass Pathways is also running two Phase III trials on its synthetic psilocybin, COMP360, in TRD. Previously, a topline readout from the late-stage COMP005 study (NCT05624268) sent the company’s stock crashing 50%, despite the study meeting its primary endpoint, with patients experiencing an average 3.6-point reduction in MADRS scores during the trial.
GlobalData, parent company of Clinical Trials Arena, previously identified a 500% surge in psychedelic drug development partnership deals between 2019 and 2023, highlighting the increased interest in such therapies.
