A new clinical trial is offering hope for individuals struggling with treatment-resistant depression. Researchers have found that vaporized N,N-Dimethyltryptamine (DMT) may provide rapid and sustained relief from symptoms, potentially offering a significant advancement over existing treatments.
Depression affects over 185 million people worldwide, and approximately one-third of those cases are classified as treatment-resistant, meaning they don’t respond adequately to conventional antidepressants. Current oral antidepressants often take weeks to show effects, and crucially, don’t offer immediate relief from suicidal thoughts. This urgent need for faster-acting therapies has driven research into psychedelics, but many have limitations.
Psychedelics like psilocybin and ayahuasca have shown promise in alleviating depressive symptoms, but their long duration of action – several hours – can make them impractical and costly for widespread use in public health systems. DMT, a naturally occurring psychedelic also found in ayahuasca, presents a potential solution. It has a much shorter duration – typically 10 to 20 minutes – and can be administered non-invasively through inhalation.
Unlike ayahuasca, which contains monoamine oxidase inhibitors (MAOIs) that can cause dangerous drug interactions, vaporized DMT doesn’t carry the same pharmacological risks. A recent phase 1/2 trial, published in Nature, evaluated the safety and efficacy of inhaled DMT in 14 patients with treatment-resistant depression. The study used a fixed-order, dose-escalation design, administering either 15 mg or 60 mg of the vaporized DMT formulation (GH001).
The results were encouraging. The treatment was found to be safe and well-tolerated, with manageable psychedelic effects and no serious adverse events reported. Even patients who continued to take antidepressants during the trial experienced similar safety outcomes. Importantly, the study demonstrated a rapid reduction in depressive symptoms. On average, participants experienced a 21.14-point reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) by day 7 (p < 0.001). The MADRS is a widely used tool to measure the severity of depressive symptoms, with higher scores indicating greater depression.
The response rate – defined as a greater than 50% reduction in MADRS score – was 85.71%, and the remission rate – defined as an MADRS score of 10 or less – was 57.14% seven days after administration. Remarkably, these improvements were sustained for up to three months in some patients. The trial also showed a significant decrease in suicidal ideation, with no participants reporting severe suicidal thoughts the day after receiving the DMT.
Another ongoing trial, registered on ClinicalTrials.gov (NCT06094907), is further investigating the safety, tolerability, and antidepressant effects of inhaled DMT. This phase II open-label study is assessing the feasibility of using DMT in a clinical setting.
A separate, phase IIa randomized, placebo-controlled trial, also reported in Nature, evaluated intravenous DMT for major depressive disorder. This trial, sponsored by Small Pharma (now Cybin UK), involved a two-stage, double-blind, randomized, placebo-controlled design with 34 participants. Participants received either DMT fumarate or a placebo, accompanied by psychotherapeutic support focused on psychological flexibility.
The trial design involved two stages. In stage 1, participants were randomly assigned to receive either DMT or placebo. Two weeks later, in stage 2, those who received placebo in stage 1 received DMT, while those who received DMT in stage 1 received a second dose. Participants who declined a second dose were still followed up. The dose administered was 21.5 mg of DMT fumarate, infused intravenously over 10 minutes.
The study emphasized the importance of a controlled setting and therapeutic support. Participants were admitted to a ward the day before dosing and received preparation sessions with two therapists, including guided visualization and discussion of expectations. During dosing, participants wore eyeshades and listened to curated ambient music, while two therapists provided silent support. Following the DMT session, participants received integration sessions to help them process their experiences and apply insights to their daily lives.
Researchers also conducted a thorough assessment of safety and tolerability, monitoring blood pressure, heart rate, and conducting ECGs. Adverse events were categorized by severity and relationship to treatment. Participants were also asked if they regretted the experience, providing further insight into tolerability.
While the results are promising, it’s important to note that this research is still in its early stages. The trials have involved relatively small sample sizes, and further research is needed to confirm these findings in larger and more diverse populations. The long-term effects of DMT treatment are still being investigated. A six-month follow-up visit was included in the study to monitor long-term outcomes.
Another trial (NCT06816667), detailed on ClinicalTrials.gov, is evaluating the safety, tolerability, and efficacy of multiple sublingual microdoses of 5-MeO-DMT in reducing symptoms of depression and/or anxiety. This Phase 1/2 randomized, double-blind, placebo-controlled trial represents another avenue of investigation into the potential of psychedelic-assisted therapy.
Despite the need for further research, the initial findings suggest that vaporized DMT could offer a novel and effective treatment option for individuals with treatment-resistant depression, potentially providing rapid relief and improving quality of life. The combination of DMT with a supportive therapeutic framework appears to be a crucial element in maximizing benefits and ensuring patient safety.
