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Clinical Trial of DMT for Depression Announces “Positive” Early Data

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A Phase IIa clinical trial of DMT (dimethyltryptamine) for the treatment of major depressive disorder (MDD) has announced positive preliminary findings from the trial’s 6-month data.

The data, which have not yet been peer-reviewed, suggest that some patients with MDD may benefit from treatment with the short-acting psychedelic compound alongside supportive therapy.

DMT and major depression

DMT is a strong but relatively short-acting psychedelic compound that is rapidly metabolized by the body. It produces short but intense psychedelic “trips” that can induce hallucinations while also affecting the user’s thinking, mood and sense of time.

DMT has long been used in traditional rituals and ceremonies in Central and South America – it is naturally produced by several plant species and is also the key psychedelic ingredient in the hallucinogenic brew ayahuasca. However, in recent years, the therapeutic potential of DMT and other psychedelics – such as psilocybin, the psychoactive ingredient in “magic mushrooms” – has been increasingly recognized for psychiatric disorders such as MDD.

Now, biotechnology company Small Pharma has reported positive early results from a trial of their proprietary, pharmaceutical-grade synthetic DMT formulation – known as SPL026 – in patients with MDD.

“Encouraged” by early data

The Phase IIa study – involving 34 participants with moderate to severe MDD – was designed to test the safety and efficacy of SPL026.

The study was split into two stages – first, a blinded, randomized and placebo-controlled trial conducted over two weeks. Participants received either a single intravenous dose of 21.5 mg SPL026 – resulting in a 20–30-minute psychedelic experience – or a placebo, both of which were given alongside supportive therapy.

In the second, open-label (unblinded) stage, all participants received a single dose of SPL026 with supportive therapy and were followed up over a 3-month period.

At the end of the three-month period following the open-label dose, some patients continued to be followed up “out-of-study” for six months. In total, 25 patients completed the additional 6-month follow-up period. This allowed the study team to assess to what extent the treatment could bring about a lasting effect, using a diagnostic questionnaire called the Montgomery–Åsberg Depression Rating Scale (MADRS). The MADRS is a ten-question rating scale developed used by clinicians and psychiatrists to measure the severity of depression symptoms.

Data released by Small Pharma suggests that 14 out of the 25 patients that completed the 6 months of additional follow-up had achieved remission within the initial 3-month study period.

What is remission?

Remission is defined as either a partial or full reduction in depressive symptoms, though it is not necessarily a complete recovery from MDD. Small Pharma defined remission as a MADRS score ≤10.

Of those 14 “prior remitters”, 9 patients (64%) remained in remission at 6 months. Additionally, out of all 25 patients that completed the 6-month follow-up, 10 patients (40%) met the criteria for remission.

“This new data shows that the antidepressant effect was sustained for six months in two-thirds of patients who were in remission at an earlier time-point in the study,” said Dr. Carol Routledge, chief medical and scientific officer at Small Pharma. “As we finalize the design of the Phase IIb study, this data helps to inform our understanding of treatment durability and our approach to patient retreatment within the trial.”

Informing further trials

“We are pleased to see that participants in our study experienced durable relief from their depression for an extended period of time,” added George Tziras, chief executive officer at Small Pharma. “Given these clinical outcomes from one or two treatments, this could further offer potential value to healthcare systems that face challenges with patients who struggle to adhere to their daily antidepressant use.”

Despite this announcement of positive preliminary data from some patients, a number of participants did not achieve remission after the treatment. Additionally, without a suitable long-term comparison group it is not possible to rule out whether other factors involved in MDD aside from the treatment may be responsible for their improvement. Overall, this Phase IIa trial may pave the way for additional, more robust trials to investigate the efficacy of SPL026 for the treatment of MDD.