A recent study suggests that the positive emotional states experienced during MDMA-assisted therapy for post-traumatic stress disorder might play a central role in helping patients recover. The findings indicate that although patients occasionally have full mystical experiences under the influence of the drug, these profound states do not seem to be the primary driver of symptom relief. The research was published in Journal of Psychopharmacology.
Scientists have gathered evidence that classic psychedelics, such as psilocybin and LSD, tend to improve mental health by triggering profound alterations in human consciousness. For example, a 2022 systematic review showed that when patients have deeply spiritual or mystical experiences during psychedelic therapy, they often experience greater reductions in psychiatric symptoms across various disorders. These mystical states typically involve a sense of unity with the universe, an inability to describe the event in words, and a deep sense of positive mood.
The mechanism behind MDMA, a different type of psychoactive substance, seems to operate differently. A study covered by PsyPost in 2019 noted that MDMA combined with psychotherapy safely and effectively reduced PTSD symptoms, with half of the treated patients no longer meeting the diagnostic criteria for the disorder. A later 2021 clinical trial confirmed these benefits for people with severe PTSD, prompting questions about exactly what happens during the therapy sessions to drive such recovery.
“People often place MDMA and classic psychedelics such as psilocybin and LSD in the same broad category, but the experiences they produce can be quite different,” explained lead author Tijmen Bostoen, a psychiatrist and researcher at ARQ Centrum ’45 and a doctoral candidate at Leiden University Medical Center. “In therapy with classic psychedelics, mystical or transcendent experiences are often thought to play an important role in clinical improvement. We wanted to test whether mystical-type experiences also play such a role in MDMA-assisted therapy for PTSD.”
To answer this question, the research team analyzed data from two previous clinical trials. The team examined 53 participants who suffered from chronic, treatment-resistant PTSD, meaning their symptoms had not improved after standard therapies. The participants underwent a structured therapy program that included three preparatory counseling sessions. Following preparation, they completed two eight-hour drug-assisted therapy sessions spaced a few weeks apart, and multiple integration sessions to process their experiences.
During the drug-assisted sessions, participants were randomly assigned to receive either a standard therapeutic dose of MDMA or an active placebo. The standard group received doses ranging from 75 to 125 milligrams. The active placebo group received a very low dose of MDMA of either 30 or 40 milligrams, which was meant to mimic the initial physical sensations without providing the full psychological effect. The therapy took place in a comfortable room where patients listened to music and focused inward, with two therapists present to provide support.
To measure the intensity of the subjective drug effects, the researchers had participants complete a 30-item Mystical Experience Questionnaire the day after each dosing session. This questionnaire rates experiences across four categories: a general mystical feeling of unity, a deeply felt positive mood, a sense of transcending time and space, and ineffability, meaning the experience is hard to put into words. To evaluate the treatment’s success, independent evaluators assessed the severity of the participants’ PTSD symptoms before the therapy began and one month after the second dosing session using a standardized clinical interview.
Bostoen and his colleagues found that the standard doses of MDMA prompted much stronger mystical-type experiences than the low-dose active placebo. Participants in the standard dose group scored an average of 63.1 points on the mystical experience questionnaire, representing about 42 percent of the maximum possible score. In contrast, the active placebo group averaged just 24.7 points, or about 16 percent of the maximum score.
About 23 percent of the participants receiving the standard dose met the formal criteria for having a complete mystical experience during at least one of their sessions. None of the participants in the active placebo group reached this threshold. The standard dose group also saw much larger drops in their PTSD symptoms, with average symptom severity scores dropping by about 36 points on a 136-point scale. The placebo group experienced an average drop of about 15 points.
When the researchers tested whether the mystical experiences directly explained the drop in PTSD symptoms, the overall questionnaire scores were not statistically significant mediators. “I expected mystical-type experiences to play some role in MDMA-assisted therapy, perhaps less strongly than in therapy with classic psychedelics, but still meaningfully,” Bostoen told PsyPost. “It was therefore surprising that the overall mystical experience score did not significantly mediate PTSD symptom improvement.”
Instead, only one specific component of the experience seemed to drive the therapeutic benefit. The positive mood subscale of the questionnaire, which measures feelings of joy, peace, and love, was the only factor that reliably linked the MDMA treatment to the improvement in PTSD symptoms.
“This suggests that MDMA-assisted therapy may be less about transcending the self, and more about creating an emotionally open and positive state in which people with PTSD may be able to relate to themselves, others, and traumatic memories differently,” Bostoen explained.
“This was a secondary analysis of existing clinical trial data, and the original studies were not specifically designed to answer this mechanistic question,” Bostoen noted. “The sample size was modest, so the findings should be interpreted cautiously and need replication.” The sample was also overwhelmingly white, meaning the results might not perfectly reflect how diverse populations experience the therapy.
Because the questionnaire was originally designed for classic psychedelics, it might not fully capture the unique sensations of connection and empathy that MDMA produces. “It may be that mystical-type experiences are not the best framework for understanding MDMA-assisted therapy,” Bostoen said. “Future studies should examine MDMA-specific processes more directly, such as emotional openness, positive affect, self-compassion, empathy, interpersonal connection, and the ability to engage with traumatic memories without becoming overwhelmed.”
“Many people who have clinical or personal experience with these substances already sense that MDMA feels different from classic psychedelics such as psilocybin or LSD,” Bostoen added. “The findings suggest that we should not assume that all psychedelic-assisted therapies work through the same psychological mechanisms.”
The study, “The occurrence and potential role of mystical experiences in MDMA-assisted therapy for PTSD: A secondary analysis,” was authored by Tijmen P.L. Bostoen, Erwin Krediet, Annette M. van Schagen, Nic J.A. van der Wee, and Erik J. Giltay.