In an early clinical trial, a single dose of a short-acting psychedelic drug led to rapid improvement in people with major depressive disorder.
The study included 34 patients with moderate-to-severe depression, all of whom had tried other treatments without success. Those given a single intravenous dose of dimethyltryptamine (DMT) showed significant improvement within a week compared to those who received a placebo.
Unlike psilocybin and lysergic acid diethylamide ( LSD), whose effects can last for hours, intravenous DMT has a half-life of around five minutes. Its psychedelic effects are correspondingly brief, potentially making it more practical to administer in clinical settings.
"A single dose of DMT with psychotherapeutic support produced a rapid, significant reduction in depressive symptoms, sustained up to three months," writes a team led by neuroscientists David Erritzoe and Tommaso Barba of Imperial College London.
Major depressive disorder is one of the leading causes of disability worldwide. While many patients are treated with antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), a substantial proportion either do not respond adequately or experience side effects that make long-term treatment difficult. This has fueled growing interest in alternative approaches.
Psychedelic drugs that act on serotonin receptors linked to depression have shown promise in clinical trials, but their hours-long effects can make them challenging to administer in clinical settings.
Traditional psychedelic-assisted therapy sessions can last most of a day and sometimes require multiple clinicians present throughout.
By contrast, the psychedelic effects of intravenous DMT are brief, lasting minutes rather than hours. This might present a much more viable treatment option, but DMT's effects on the symptoms of depression had not been quantified. This is what Erritzoe and his colleagues sought to address.
They recruited 34 participants with major depression and divided them into two groups of 17 for a double-blind, placebo-controlled trial.
In the first stage of the trial, one group received an intravenous dose of DMT, while the other received an active placebo. Neither the researchers nor the participants were informed which participants received the DMT.
The doses took around 10 minutes to administer, and a therapist sat with each participant to ensure comfort and safety while the psychedelic effects were active, remaining silent throughout the treatment.
The treatment was generally well tolerated. Most side effects were mild to moderate, and included nausea, temporary anxiety, and pain at the injection site. No serious adverse events related to the treatment were reported, although brief increases in heart rate and blood pressure were observed immediately after dosing.
In the second, open-label stage, two weeks after the first dose, all participants were given the opportunity to receive a dose of DMT.
Participants were assessed before and at intervals after each dose using the Montgomery-Åsberg Depression Rating Scale. Just a week after the first dose, participants who had received DMT had improved scores compared to the placebo group, and improvements were sustained during follow-up assessments.
Two weeks after the first dose, the participants who received DMT scored about seven points lower, on average, than those who received a placebo. On this commonly used clinical scale, a drop of that size is generally considered a meaningful reduction in symptom severity.
There was no significant difference between patients who received one or two doses of DMT, suggesting a single dose may be sufficient.
These effects persisted for up to three months, and some patients remained in remission for at least six months following the treatment.
Related: Psilocybin Breaks Depressive Cycles by Rewiring The Brain, Study Suggests
Now, there are some caveats. The obvious psychedelic effects of DMT may have compromised the double-blinding, and the study did not assess whether participants could guess which treatment they received. The trial also included only 34 participants.
Still, the findings suggest that short-acting psychedelics may warrant further investigation as a potential treatment for people whose depression has not responded to conventional therapies.
"Longer and larger trials, including comparisons with existing treatments, are needed to further evaluate the efficacy, safety, and cost-effectiveness of DMT in the treatment of major depressive disorder," the researchers write.
The findings have been published in Nature Medicine.