A recent study conducted in Norway suggests that MDMA-assisted therapy may provide lasting relief for individuals suffering from major depressive disorder. The findings indicate that the clinical benefits observed immediately after treatment were largely sustained several months later. This research provides preliminary evidence that the intervention is feasible and generally safe for this patient population. The study was published in the Journal of Psychiatric Research.
Major depressive disorder creates a significant burden on global health. It affects hundreds of millions of people and is a leading cause of disability. While current treatments such as antidepressants and standard psychotherapy are effective for many, they do not work for everyone. Approximately one-third of patients do not find relief even after trying multiple medication regimens.
Many patients who do improve eventually experience a return of their symptoms. Research indicates that maintaining a long-term response often requires ongoing therapy, which can be difficult to access or maintain. Past large-scale studies have shown that remission rates can be quite low for those with resistant forms of depression. Consequently, there is a pressing need for novel treatment approaches that offer durable efficacy.
MDMA, often referred to as ecstasy or molly when used recreationally, is a chemical compound known scientifically as 3,4-methylenedioxymethamphetamine. It acts as a stimulant and has properties that can elevate levels of serotonin in the brain. In controlled clinical settings, the effects of the drug are notably different from its recreational use. The substance tends to enhance feelings of empathy and self-compassion.
These subjective effects are thought to create a favorable state for psychotherapy. They may allow patients to identify and regulate difficult emotions more effectively. The therapeutic approach used in conjunction with the drug is often described as “inner-directed.” This means the therapy relies on the patient’s innate capacity for recovery and processing.
“Major depressive disorder remains one of the most common and disabling mental health conditions, and many patients do not achieve lasting relief with existing treatments. While MDMA-assisted therapy has shown promising results in late-stage trials for PTSD, there has been very limited clinical research on MDMA-assisted therapy specifically for depression,” said study author Tor-Morten Kvam, a consultant psychiatrist at the Ketamine Unit at Østfold Hospital Trust and PhD candidate at the University of Oslo.
“We wanted to address this gap by exploring whether MDMA-assisted therapy could be delivered safely and feasibly to people with primary MDD, and whether potential benefits might persist beyond the immediate treatment period.”
To investigate this, the research team recruited twelve participants. All participants were eighteen years of age or older. They were all diagnosed with major depressive disorder of at least moderate severity. The participants had been experiencing their current depressive episode for more than three months but less than two years.
The study took place at a single hospital site in Norway. The researchers employed an open-label design. This means that both the medical staff and the patients were aware that the active treatment was being administered. There was no placebo control group in this specific trial.
The treatment protocol involved two medication dosing sessions. These sessions were spaced approximately one month apart. During the first session, participants received an initial dose of 80 mg of MDMA. A supplemental dose of 40 mg was offered about two hours later.
The second session utilized a slightly higher dosage. Participants received 120 mg initially, followed by a 60 mg supplemental dose. These dosing sessions were not standalone events. They were integrated into a broader course of psychotherapy.
Participants attended a total of nine 90-minute therapy sessions. These sessions served to prepare the patients for the experience and to help them integrate the psychological material that emerged. The follow-up assessment occurred seven months after the start of the study. This was four months after the entire treatment course had concluded.
The primary measure used to track progress was the Montgomery-Asberg Depression Rating Scale. This is a clinician-rated tool designed to assess the severity of depressive symptoms. The raters were independent of the immediate study team to reduce bias, though they were not formally blinded to the treatment.
The secondary outcome measure was the Sheehan Disability Scale. This tool evaluates how much the patient’s condition impairs their daily functioning. It looks at occupational, social, and domestic areas of life. The researchers also used several exploratory measures to assess anxiety, sleep quality, and symptoms of trauma.
The results showed that all twelve participants completed the seven-month follow-up visit. The data indicated a significant reduction in depression scores at the follow-up point compared to the baseline. The improvement seen immediately after treatment appeared to be sustained over the longer term.
Specifically, nine of the twelve participants were classified as responders immediately after the treatment ended. At the seven-month mark, eight of those participants maintained that response. Similarly, nine participants were considered to be in remission after treatment. Eight of these individuals remained in remission at the follow-up.
“One striking aspect was how durable the improvements appeared to be for many participants, even six months after the final MDMA dosing session—lasting beyond the dosing sessions and the structured therapy period,” Kvam told PsyPost. “We also saw that while most participants improved, a small subset did not respond or experienced relapse, which highlights that this approach may not work for everyone.”
Only one participant who initially achieved remission experienced a relapse during the follow-up period. The three participants who did not respond to the treatment initially did not show spontaneous improvement later. The researchers found no significant changes in symptom scores between the immediate post-treatment assessment and the seven-month follow-up. This suggests that the therapeutic gains were stable during the period without active therapy.
In addition to depression symptoms, the participants reported improvements in other areas. The study found significant reductions in scores related to functional impairment. Participants also reported better sleep quality and lower levels of generalized anxiety.
Safety was a key focus of the study. The researchers closely monitored for suicidal ideation and behavior. They used the Columbia-Suicide Severity Rating Scale for this purpose. The results showed that mean scores for suicidal ideation did not exceed the levels observed before the study began.
No serious suicidal behavior occurred during the study or the follow-up period. However, two participants who did not respond to the treatment reported an increase in the intensity of suicidal thoughts at the follow-up. One participant with a history of suicide attempts reported preparatory behavior but did not make an attempt.
These findings regarding safety are consistent with observations from PTSD trials. The researchers suggest that a third dosing session might be beneficial for some patients. Additional sessions could allow for further processing of difficult material that arises during therapy.
There were no dropouts in the study. This retention rate is notably higher than what is often seen in standard depression trials. Typical studies of psychotherapy or medication for depression often see higher rates of participant attrition. The lack of dropouts may suggest that the treatment was well-tolerated by the participants.
“The main takeaway is that, in this small study, participants who received MDMA-assisted therapy showed preliminary evidence of sustained efficacy and longer-term safety at seven months after baseline in this clinical setting,” Kvam explained. “At the same time, this was an early-stage open-label study, so the findings are promising but need confirmation in larger randomized controlled trials.”
The most significant limitations are the small sample size and lack of a control group, which makes it difficult to draw definitive conclusions about efficacy. Without a placebo group, it is impossible to rule out the influence of participant expectations. It is also possible that some improvement was due to the natural course of the illness.
“A key caveat is that this was an open-label study without a control group, and participants entered the trial with at least moderate depression,” Kvam noted. “This means we can’t rule out natural symptom fluctuations over time — including ‘regression to the mean,’ where symptoms may improve simply by moving from an unusually severe period back toward a more typical level.”
“The findings should also not be interpreted as evidence that MDMA is a stand-alone antidepressant, or that it is safe or effective to use outside a controlled clinical setting. We followed a strict protocol within a structured therapeutic framework—including preparation, monitoring, and integration—which likely plays a central role in both outcomes and safety.”
Despite these limitations, the study offers proof of principle. It indicates that MDMA-assisted therapy can be delivered safely to patients with major depression. The sustained nature of the improvements supports the potential of this treatment model.
“In the short term, our goal is to publish additional findings from this study, which should be available in the coming months,” Kvam said. “In the medium term, we plan to run another fully funded open label trial with a limited sample size to build on what we’ve learned so far. Over the longer term, we hope to conduct a randomized controlled trial to more clearly determine efficacy. Ultimately, our goal is to contribute high-quality evidence that can clarify whether and how MDMA-assisted therapy could fit into future care pathways for treatment-resistant depression.
“This study adds early clinical evidence to a rapidly developing field, but it also reinforces that careful screening, support, and follow-up are essential. If MDMA-assisted therapy is to have a role in depression treatment, it will need to be implemented with the same rigor and safeguards as any other specialized intervention. We hope these results contribute to a balanced discussion; recognizing both the potential and the uncertainties that remain.”
The study, “MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial,” was authored by Tor-Morten Kvam, Ivar W. Goksøyr, Justyna Rog, Inger-Tove Jentoft van de Vooren, Lowan Han Stewart, Ingrid Autran, Mark Berthold-Losleben, Lynn Mørch-Johnsen, René Holst, Jan Ivar Røssberg, Ingmar Clausen, and Ole A. Andreassen.
