- Depression is a persistent mood disorder marked by chronic feelings of emptiness and a loss of interest in activities, which can significantly impact a person’s daily life.
- Treatments, including psychotherapy, antidepressant medications, and lifestyle changes, can be effective, but some depression does not respond to these treatments.
- Now an early study has found that a single treatment with a short-acting psychedelic drug, dimethyltryptamine (DMT), can relieve severe depressive symptoms for up to 6 months.
- Experts caution that while this phase 2 study is encouraging, further research is needed to verify the findings and assess potential adverse effects.
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Now, a phase 2 trial, led by scientists from Imperial College, London, has found that treatment with another psychedelic, dimethyltryptamine, or DMT, alongside psychotherapy, can relieve severe depressive symptoms.
The study, published in
DMT is a short-acting hallucinogenic psychedelic compound that can be extracted from many different plants. It is used in traditional shamanistic compounds, such as ayahuasca, in South America and, more recently, as a recreational drug in Europe and North America.
In this phase 2 trial, researchers recruited 34 participants with a mean age of 32.8 years, who had experienced depression for, on average, 10.5 years. All participants completed the Montgomery–Åsberg Depression Rating Scale (MADRS) to measure symptom severity. Researchers then randomly divided them into two groups of 17 — treatment group and placebo.
The treatment group received 21.5mg of DMT fumarate by intravenous infusion over 10 minutes, the control (placebo) group received an identical intravenous infusion without DMT. All participants also received supportive psychotherapy for 2 weeks after the treatment.
After 2 weeks, both groups received an infusion of DMT. Researchers followed them up at regular intervals for 3 months, with participants completing the MADRS at 1, 2, 3, 4, 6 and 14 weeks, and 6 months after the first treatment.
Within one week of the first treatment, the DMT group had an average 10.8 point larger drop in MADRS scores than the placebo group. After 2 weeks, the average difference was 7.4 points.
In a second stage of the trial, both groups received DMT. The placebo group showed similar symptom improvement to that seen in the treatment group in the first stage, but there was no further improvement in the two-treatment group.
The researchers suggest that a single dose may be sufficient to achieve the antidepressant effect.
Lasting effects with a single dose
“We have shown that a single DMT experience of just around 25 minutes duration is safe, effective and durable, with effects comparable to other promising psychedelic treatments often requiring much longer treatment sessions.”
— David Erritzoe, lead investigator on the trial, from Imperial’s Department of Brain Sciences
The researchers acknowledge that these are very early results, and that their study had some limitations, including a lack of ethnic diversity and the exclusion of anyone with a history of serious suicide attempts.
They called for “longer and larger trials to further evaluate the efficacy, safety, and cost-effectiveness of DMT-assisted therapy compared with existing standard treatments.”
While welcoming the findings, James Rucker, consultant psychiatrist and senior clinical lecturer at King’s College, London, who was not involved in the study, sounded a note of caution:
“One tends to see large effect sizes in phase 2 trials, which aren’t a true test of effectiveness for various reasons. I would like to see phase 3 trials conducted in hundreds of patients and done in many different centres in different countries to be more reassured about the effectiveness and safety profile of DMT.”
Erritzoe emphasized that early trial results should always be interpreted with caution, but “they hold great promise for DMT therapy as a potential treatment for clinical depression. It is also likely to be more cost-effective than longer-acting psychedelics due to the shorter dosing sessions.”
Rucker echoed the calls for further trials, adding that although the psychedelic experience of DMT “is shorter, it also tends to be much more intense. This intensity can lead to a form of psychological shock that means that patients then need more therapeutic sessions after the dosing to help them understand and integrate the experience. This could very well offset any cost savings seen on the dosing day.”
“Psychedelics are powerful psychoactive drugs. The drug, the patient and the therapeutic setting all need to be contained and controlled to maximise safety. This is why recreational use of psychedelics can go so tragically wrong sometimes.”
— James Rucker, consultant psychiatrist
“Thus, you can think of the psychedelic therapy in trials like this as being akin to a gamble where the dice are loaded by the controlled, therapeutic setting. It doesn’t necessarily mean it will turn out well, but we do our best to maximize the chances,” Rucker added.