MDMA has shown promise for the treatment of severe post-traumatic stress disorder (PTSD) when combined with therapy.
The powder form of ecstasy, MDMA is an illegal class A drug in the UK.
In a late-stage clinical trial – often the final step before seeking drug approval – scientists from the Multidisciplinary Association for Psychedelic Studies (MAPS) in California analysed 90 patients who had endured the disorder for around 14 years.
After just three sessions of MDMA combined with therapy, nearly nine in 10 (88%) experienced a "clinically meaningful reduction in symptoms".
In addition, just over two-thirds (67%) "no longer qualified for a PTSD diagnosis".
Therapy often forces a PTSD patient to recall their previous trauma, while MDMA has the "unique ability" to "raise compassion and understanding while tamping down fear", according to the study's lead author Dr Jennifer Mitchell.
The MAPS results come after scientists from Imperial College London found a psychedelic compound in magic mushrooms is at least as effective as a commonly prescribed antidepressant.
The preliminary results are expected to be published in the journal Nature Medicine.
"The experience of having been traumatised profoundly alters perceptions, self-experience, and capacity to plan, imagine and anticipate," said study author Dr Bessel van der Kolk.
"For 88% of people who receive this treatment, we can expect to see a treatment response.
"This can lead to fundamental shifts in our subjects' perspective on self-capacity, affect regulation and attitude towards those around them.
"It takes a great deal of courage to address one's PTSD, particularly when other treatments have failed.
"These results open the door to a potentially powerful new pathway to healing, once MDMA-assisted therapy has been approved as a treatment for PTSD."
The MAPS scientists believe the US Food & Drug Administration (FDA) could approve the MDMA-therapy regimen for severe PTSD as soon as 2023.
PTSD is thought to affect one in three people who "have a traumatic experience". Up to half of patients do not find relief from existing treatments, typically antidepressants and therapy.
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The study's 90 participants developed PTSD after enduring a range of traumatic incidents, like "combat-related events", abuse and "sexual harm".
Forty-six received MDMA, while the remaining 44 were given a placebo, with both groups also having "identical talk therapy". It is unclear how the drug was administered.
Eighteen weeks later, 67% in the MDMA group no longer met the diagnosis for PTSD, which often causes a patient to relive their traumatic experience via nightmares and flashbacks. This is compared to under a third (32%) of those on placebo.
A clinically significant reduction in symptoms was experienced by 88% on MDMA versus 60% in the placebo group.
The MDMA participants also experienced a significant improvement to their "functional impairment" relative to those on a placebo.
"People with the most difficult-to-treat diagnoses, often considered intractable, respond just as well to this novel treatment as other study participants," said Dr Mitchell.
"Participants diagnosed with the dissociative subtype of PTSD experienced a greater reduction in symptoms than those without the dissociative subtype."
Dissociative PTSD is generally "marked by symptoms of derealisation", like a patient feeling like they are in a dream.
Trial participant Scott Ostrom, 36, endured nightmares for more than decade after returning from a second deployment in Iraq in 2007.
Speaking of his nightmares, Ostrom told The New York Times: "Bullets would dribble out of the end of my gun, or I'd get separated from my team and be lost in a town where insurgents were watching me."
Approved treatments and therapy alone did not help. After taking part in the MAPS trial, Ostrom said: "Literally, I’m a different person."
Although it is unclear exactly how the MDMA-therapy regimen works, Dr Mitchell said: "MDMA is an experiential therapeutic, and therefore necessitates the appropriate set and setting to truly guide change and recovery.
"While many forms of PTSD therapy involve recalling previous trauma, the unique ability of MDMA to raise compassion and understanding while tamping down fear is likely what enables it to be so effective."
MDMA is thought to raise levels of feel-good chemicals in the brain, much like antidepressants. The illegal substance is expected to have no benefit when taken without therapy.
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When it comes to safety, "no serious issues" occurred in the trial.
As expected, taking MDMA caused a temporary increase in a patient's blood pressure and heart rate. They also endured "transient" muscle tightness, appetite reduction, nausea, sweating and a sense of being cold.
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MDMA is a Schedule I drug in the US, with officials stating it has "no medical benefit".
"As a result of this study, and through the persistent and consistent application of scientific rigour, we have demonstrated MDMA-assisted therapy is likely to provide relief for people diagnosed with PTSD," said Dr Rick Doblin, MAPS' executive director.
"Far from having no medical benefit, MDMA – when combined with talk therapy in this protocol – has the potential to catalyse the therapeutic process and generate positive mental health outcomes."
The scientists are recruiting patients for a second phase three trial.
Prior to hopeful FDA approval, the administration has signed off an expanded access programme where 50 patients can receive the MDMA-therapy regimen.
The MAPS scientists plan to carry out additional studies testing the drug's potential for other mental health conditions.
While the trial results may sound promising, not everyone is convinced.
Professor Allen James Frances from Duke University has warned new treatments "are never as wonderful as first they seem".
"All new treatments in medicine have always had a temporary halo effect by virtue of being new and by promising more than they can possibly deliver," he told The New York Times.