U.S. approval for psychedelic drug MDMA nears after success in clinic

MDMA clinical trials

The psychedelic drug MDMA edges closer towards FDA approval for the treatment of post-traumatic stress disorder (PTSD) in the U.S., after promising results of a trial were published. 

This comes after Australia became the first country to allow doctors to prescribe the drug to those struggling with mental health disorders like PTSD and depression. 

Recognizing that this could be a turning point in mental health research, Mustafa Tai, psychiatrist and medical director at U.S.-based mental healthcare provider PsychPlus said: “This could encourage other countries to take a hard look at legalizing these types of medications as well.”

PTSD worldwide: prevalence and treatment challenges

PTSD affects around 3.6% of the world’s population, according to a report published by the World Health Organization (WHO) in 2013. This means that over 280 million people live with the condition. However, these numbers don’t account for the many cases that go undiagnosed, often due to the lack of access to mental health care and stigma in various parts of the world.

Classified as an anxiety disorder, PTSD occurs when people experience or witness a distressing event or series of events, which can translate into people reliving that trauma through flashbacks and nightmares. 

Apart from talking therapy and cognitive behavioral therapy, a type of antidepressant known as selective serotonin reuptake inhibitors (SSRIs), which boost serotonin levels in the body, are typically prescribed for PTSD. But only two have received the U.S. Food and Drug Administration (FDA) nod so far. Serotonin, sometimes referred to as the ‘happy hormone’, is a chemical that regulates mood and appetite. 

However, the dearth of novel contenders in the past couple of decades limits treatment options for patients.

But, the success of MDMA in clinical trials, a drug that was outlawed in the last century, could change things for people with PTSD in the U.S..

MDMA: what changed with the ban?

3,4-methyl​enedioxy​methamphetamine (MDMA), also known as Ecstasy and Molly, is an ‘empathogenic’ drug, which means it facilitates a feeling of connectedness between individuals, which is beneficial in a therapy setting to allow an individual with PTSD to really explore and express their feelings and emotions, Amy Recihelt, neuroscientist and chief innovation officer at PurMinds NeuroPharma told Labiotech.

The drug, which was developed by multinational pharmaceutical company Merck in the early 20th century, gained a small following of psychiatrists in the late 1970s and 80s. But the Drug Enforcement Administration’s (DEA’s) emergency ban in 1985, classifying it as a Schedule 1 drug – a drug that is thought to have no therapeutic value – forced many who used the drug to combat trauma to switch to other forms of therapies, despite claims suggesting that MDMA had therapeutic potential.

Since then, various organizations and biopharmas have been racing to prove the drug’s worth. In 2017, the FDA granted the drug ‘breakthrough therapy’ status as a treatment for PTSD, along with psilocybin, the active ingredient in ‘magic mushrooms.’ This put both drugs on the radar for a fast-tracked approval. 

Clinical trial puts MDMA-assisted therapy en route to FDA approval

Advocating to legalize MDMA-assisted therapy, the American nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), has steered the move to getting the approval from the FDA. It published recent phase 3 trial results in Nature Medicine, last week.

Participating in the trial were 104 people who had been diagnosed with moderate to severe PTSD for about 16 years. Among this patient cohort were war veterans, victims of childhood abuse, and survivors of sexual assault. For the trial, the participants received talking therapy followed by MDMA-assisted therapy or the placebo, over three months.

By the end of the study, 86.5% of the people in the MDMA-assisted therapy group achieved a meaningful improvement in the severity of their PTSD symptoms. Moreover, over 71% of the people in the MDMA-assisted therapy group had a reduction in symptoms, to the extent that they no longer qualified for a PTSD diagnosis, compared to nearly 48% of people in the placebo group.

“The outcomes showed that using MDMA positively affected functional impairment including in participants’ personal and professional lives,” said Tai. “Amazingly, the outcomes showed that over 85% of those that took MDMA, showed clinically significant improvement. Since PTSD is notoriously hard to treat, these results are very positive.”

Echoing Tai’s thoughts, Recihelt called the trial “heroic.” “Facing the barriers of working with a Schedule 1 drug, alongside public stigma from generations told that MDMA will ‘fry your brain’ – a statement based on a piece of research with a totally different drug – MAPS’ impressive clinical results go to directly support the clinical efficacy and benefits of MDMA as a tool to improve therapeutic outcomes for those with PTSD,” said Recihelt.

This 2023 trial validates a previous MAPS study that was conducted in 2021. The outcomes of the previous trial, which had left researchers optimistic, saw that 67% of those who received MDMA-assisted therapy, no longer met the criteria for a PTSD diagnosis, compared to 32% who were given a placebo.

While both these phase 3 trials corroborate one another, the 2023 study took ethnic diversity more into account. This time around, more than a quarter of the participants were Hispanic or Latino and around 34% identified their race as other than white. This improved by 18% and 12% respectively, compared to the 2021 study. As many ethnic and racial minorities in the U.S. experience higher rates of PTSD as compared to white Americans, it was significant for a clinical trial to reflect that.

Concerns and hurdles in the path to FDA approval for MDMA

However, concerns about the ‘double-blinded’ study were brought to light. In a double-blinded trial, neither the patients nor the researchers know which group they belong to. Blinding is key to minimizing bias in a clinical setting. So, when some patients figured out which cohort they were in because MDMA prompted an intense psychedelic experience unlike the placebo, this factor was challenged. But, this was partly overcome with the help of an independent evaluator who had no idea which patient received the drug. 

Another worry that has to do with how the drug will be regulated, is with regards to its side effects. As the psychedelic can have an impact on normal brain functioning by causing a surge in neurotransmitters, it can lead to memory loss, depressed mood, confusion and anxiety, explained Joseph Tucker, chief executive officer (CEO) of Enveric Biosciences in the U.S..

“Coupled with its history of illicit use as a party drug, it was scheduled in most jurisdictions around the world as something with abuse potential, negative possible impact on the brain, and no known therapeutic benefit,” said Tucker. “The scientific community is eagerly watching the ongoing trials, but the truth is, all the data isn’t in yet.”

And, while these trials have jumped hurdles to get nearer to decriminalizing MDMA, it is not to say that it’ll be smooth sailing all the way, especially as the FDA will have to work out how to regulate the drug. As Tucker pointed out, the FDA is “doing its job to wait for conclusive evidence” before making such a significant change. And Recihelt believes that “psychedelic-assisted therapy is a paradigm shift from the standard treatment regime for mental health conditions like PTSD.”

Now, as MAPS looks to leverage this milestone to file a new drug application with the FDA, Tucker is hopeful that the data that has been released so far proves out.

“If approved by the FDA, this will mark several firsts, including the first FDA approval of a psychedelic agent and also the first time the FDA approves a drug that also requires psychotherapy,” he said. “In any event, it will be a door-opening event, hopefully ushering in an entirely new wave of much needed neuropsychiatric medicines.”

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