Helus’ DMT psychedelic touts antidepressant potential in Phase IIa study

A new mid-stage study suggests a potential breakthrough in the treatment of major depressive disorder (MDD). Helus Pharma’s experimental compound, SPL026, containing dimethyltryptamine (DMT), demonstrated a significant reduction in depression symptoms among participants who had previously found little relief from conventional treatments.

Promising Results in Phase IIa Trial

The Phase IIa trial (NCT04673383) involved 34 patients with moderate-to-severe MDD, all of whom had experienced unsuccessful treatment with at least two prior regimens, including both pharmaceutical and psychotherapy approaches. Participants were randomly assigned to receive either a 21.5mg intravenous dose of SPL026 or a placebo.

Did You Know? The study included patients who had previously failed to respond to at least two prior treatments for major depressive disorder.

One week after receiving the SPL026 dose, patients showed a substantial 10.8-point decrease in their average scores on the Montgomery–Åsberg Depression Rating Scale (MADRS), a standard measure of depression severity. This improvement was sustained at the two-week mark, with a 7.4-point reduction from baseline.

Longer-Term Effects Observed

Researchers from Imperial College London, who led the trial, also noted that the antidepressant effects of SPL026 appeared to persist in some patients for up to six months after treatment. Interestingly, the study found that a single dose of SPL026 was as effective as two doses, suggesting a simplified treatment protocol may be possible.

The compound was also found to be safe and well-tolerated, with no serious adverse events or changes in suicidal ideation reported during the study period.

The Search for ‘No-Trip’ Psychedelics

While the results are encouraging, researchers observed that the drug’s effectiveness may be linked to the intensity of the psychedelic experience it induces. This presents a challenge, as the hallucinogenic effects of psychedelics can be undesirable for both patients and clinicians, requiring carefully controlled administration and potentially deterring patients from seeking treatment.

This has spurred the development of non-psychoactive psychedelics, aiming to deliver therapeutic benefits without the hallucinogenic side effects. Delix Therapeutics is currently working on zalsupindole (DLX-001), a nonhallucinogenic neuroplastogen, with plans to initiate Phase II trials for MDD.

Expert Insight: The challenge of balancing therapeutic efficacy with patient comfort is a key consideration in psychedelic drug development, potentially influencing how these treatments are ultimately adopted in clinical practice.

Growing Industry Interest in Psychedelics

The pharmaceutical industry is showing increasing interest in psychedelics as potential treatments for mental health conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD). Helus, formerly known as Cybin, is among the companies working to commercialize psychedelic molecules for mental health applications.

AtaiBeckley is planning a Phase III trial for its mebufotenin benzoate nasal spray in treatment-resistant depression (TRD) in the second quarter of 2026, following positive Phase IIa results. Compass Pathways is also conducting Phase III trials on its synthetic psilocybin, COMP360, for TRD. GlobalData reports a 500% increase in psychedelic drug development partnership deals between 2019 and 2023, indicating a significant surge in investment and collaboration in this field.

Frequently Asked Questions

What is SPL026?

SPL026 is an experimental compound developed by Helus Pharma that contains dimethyltryptamine (DMT), a naturally occurring psychedelic.

What was the primary outcome of the Phase IIa trial?

The trial demonstrated a significant 10.8-point drop in MADRS scores one week after patients received a 21.5mg intravenous dose of SPL026, compared to those receiving a placebo.

Is SPL026 safe?

The study reported that SPL026 was safe and tolerable, with no serious treatment-emergent adverse events or concerning changes in suicidal thoughts recorded during the study period.

As research continues, will these findings pave the way for a new class of depression treatments, and what role will patient experience play in their effectiveness?