As we venture further into this new era of psychedelic innovation and discovery, more folks are becoming aware of the potential benefits of substances like psilocybin, LSD, or ketamine. But what about dimethyltryptamine, or DMT, an active chemical in the hallucinogenic plant brew ayahuasca?
U.K.-based biotech company Small Pharma is conducting the first major study of DMT and its potential for treating major depressive disorder (MDD). The company, which focuses on short-duration psychedelic-assisted therapies for mental health conditions, completed its Phase IIa clinical trial, finding a “significant and clinically relevant reduction in depression symptoms” two weeks after dosing, compared to the placebo group, according to a news release.
“SPL026 (intravenous DMT) with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable, with a remission rate of 57% at three months following a single dose of SPL026,” said Dr. Carol Routledge, Small Pharma’s chief medical and scientific officer.
Because of DMT’s short hallucinogenic duration, it’s possible the substance could be an even better clinical alternative to other psychedelics requiring longer treatment sessions.
The trial, and one of the largest for a short-acting psychedelic, involved 34 patients with moderate to severe MDD, and those who were already medicated were withdrawn from treatment prior to dosing. Participants were given a short IV fusion of 21.5 mg of intravenous DMT, resulting in a 20 to 30-minute psychedelic experience.
The two-phased study also included a blinded, randomized, placebo-controlled phase, where the primary endpoint assessed the DMT group versus the control group at two weeks post-dose. All participants were enrolled into an open-label phase of the study, which enabled the assessment of the “durability of the antidepressant effect,” along with comparative efficacy and safety of a one-dose versus a two-dose regimen of DMT.
Researchers said, following analysis of key secondary endpoints, that there was a rapid onset of antidepressant effects one week post-dose, though no apparent antidepressant effect was observed between a one- and two-dose regimen of intravenous DMT.
The intravenous dose of DMT was also well tolerated by all patients who received an active dose, with no drug-related serious adverse events, including suicidal ideation or behavior, reported.
“The results are exciting for the field of psychiatry,” said Dr. David Erritzoe, a clinical psychiatrist at Imperial College London and chief investigator of the Phase I/IIa study. “For patients who experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising.”
Small Pharma CEO George Tziras also spoke to the potential impact of the trial’s results, particularly for those hundreds of millions of people who live with MDD worldwide. Citing the greater confrontation of psychedelic medicine, addressing the decades of failure on behalf of pharmaceutical drugs, Tziras said the “scale of unmet needs” merits the further investigation of other more effective remedies.
“Our goal is to develop proprietary, scalable and reimbursable short-duration psychedelics with supportive therapy to address this need,” Tziras said. “I am delighted with our top-line results, which demonstrate proof-of-concept for SPL026 and provide encouraging support for our broader portfolio. I want to thank each patient who took part in this trial, as well as their families, the trial investigators, the employees of the trial sites and everyone who has supported the successful completion of this study.”
Research surrounding DMT, and ayahuasca, is still limited—as is psychedelic research surrounding mental health in the grand scheme—though it’s slowly beginning to amp up, as similar studies boast promising results for psychedelic treatment of otherwise treatment-resistant mental health conditions.
One recent study found that ayahuasca use, although a different experience than that of Small Pharma’s study participants, resulted in a high rate of adverse physical effects and challenging psychological effects, though they were generally not severe. In fact, the study found that many participants continued to attend ceremonies and generally perceived that the benefits overshadowed any adverse effects—88% of people surveyed considered adverse effects as an expected part of the process of growth or integration.
Next up, the detailed results of the Phase IIa trial are expected to be presented at upcoming scientific meetings and published in a peer-reviewed journal.