In a surprising turn of events, key advisors to the US Food and Drug Administration (FDA) have voted against endorsing the use of MDMA as a treatment for post-traumatic stress disorder (PTSD), stating that its effectiveness remains unproven. The independent scientific advisory committee voted 9 to 2 that human trials of the party drug did not demonstrate its efficacy, and 10 to 1 that the risks associated with MDMA outweigh its potential benefits.

Although the FDA is not obligated to follow the recommendations of its advisory committee, it often takes them into account when deciding on drug approvals. This decision sheds light on the challenges of assessing psychedelic drugs and the FDA's limited ability to evaluate psychiatric treatments.

MDMA, also known as ecstasy, is a synthetic compound known to induce euphoria and increase energy levels. It has already been approved for limited use in Australia as a treatment for PTSD and depression. The nonprofit organization Multidisciplinary Association for Psychedelic Studies (MAPS) has been conducting clinical trials and advocating for the legalization of MDMA worldwide through its commercial arm, Lykos Therapeutics.

Lykos Therapeutics developed an MDMA treatment protocol involving a series of psychotherapy sessions administered alongside three sessions in which a team of two therapists administers MDMA. The concept behind the treatment is that MDMA acts as a facilitator for patients to open up and discuss traumatic events that may otherwise be challenging to confront.

In their application to the FDA, Lykos cited two clinical trials involving around 200 individuals with PTSD, in which over 80% of those who received MDMA experienced significant improvements in their symptoms. These positive effects seemed to persist during follow-up assessments conducted between 6 and 24 months later.

However, FDA scientists expressed several concerns regarding the studies conducted by Lykos. They argued that crucial psychological and physiological safety data were lacking, and noted that participants, as well as their therapists, could frequently discern whether they had received MDMA or a placebo. The FDA report released ahead of the meeting referred to the data as "challenging to interpret."

FDA psychiatry division director Tiffany Farchione stated that the inability to blind the studies posed a significant problem. In an effort to address this issue, MAPS and the FDA agreed on a protocol in 2016 which involved an independent assessor evaluating the psychiatric progress of each participant. Nevertheless, both FDA staff and the advisory committee expressed concerns that participants' expectations of receiving the drug might affect their response to it.

Other concerns raised included the fact that a considerable portion (around 40%) of trial participants had previously used illicit MDMA, potentially introducing bias into the study sample. Additionally, some participants sought alternative treatments, including other psychedelic drugs, between the initial trial and the follow-up, making it difficult to attribute their improvement solely to MDMA.

The role of psychotherapy was also a focal point of discussion among the advisory committee members. Lykos's therapy protocol provided therapists with significant discretion in treating their clients, prompting concerns that trial participants may have received different therapy experiences depending on whether they received the drug or a placebo. The potential for a therapist's influence to make a drug appear effective was also highlighted.

The FDA emphasized that while it does not regulate therapy, it ensures that medical practitioners overseeing the drug's administration provide some form of therapy. The committee members called for strong regulations to safeguard individuals from potential abuse by clinicians while under the influence of MDMA and expressed concerns about therapist training.

The committee's vote came as a disappointment to many, including psychiatrist Rachel Yehuda from the Icahn School of Medicine, who was not on the committee. Yehuda acknowledged the valid points raised during the meeting regarding the safety of patients receiving treatment and expressed hope that the FDA would address these concerns instead of outright dismissing the drug.

Lykos responded to the vote, stating that they were disappointed but committed to ongoing collaboration with the FDA during the review process. The FDA is expected to issue a final decision on the drug's approval in August, following an investigation into allegations that participants who had negative experiences during the initial trials were discouraged from participating in the follow-up study.