Psychedelic assisted psychotherapy faces new questions in light of the FDA panel’s vote.
High hopes that psychedelic medicines were finally on the pathway to regulation were dashed last week when an FDA advisory panel voted against approving MDMA-assisted therapy for PTSD.
The decision has put a spotlight on the field—and those at the center of it—raising questions about the credibility of the research being conducted and the safety of those involved in the trials.
As far back as the 1970s, MDMA was used by mental health professionals in conjunction with talking therapy to enhance patients’ access, processing, and communication of difficult emotions and experiences.
The FDA has previously acknowledged its therapeutic potential, granting a new drug application, submitted by Lykos Therapeutics (formerly MAPS Public Benefit Corporation), priority review for drugs that, if approved, would represent “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.”
An estimated 13 million Americans are living with PTSD, including many veterans and survivors of abuse, with no new treatments having been approved by the FDA in nearly 25 years.
In January 2024, the U.S. Department of Veterans Affairs also announced it was funding research on the use of certain psychedelic compounds in treating PTSD and depression. In a press statement at the time, the VA’s Under Secretary for Health Dr. Shereef Elnahal said that veterans and VA researchers had advised on the “potential promise of psychedelics to treat mental health conditions for some time.”
The NDA includes data from two Phase 3 multi-site, randomized, placebo-controlled trials for midomafetamine (MDMA) that met their objectives.
Lykos says its clinical development program was designed in consultation with the FDA to “ensure generalizability and interpretability” of results, and its data demonstrate that midomafetamine (MDMA) leads to a “rapid, clinically meaningful, durable improvement in patients’ PTSD symptoms.”
However, following a nine-hour meeting on Tuesday, June 4, FDA advisors voted 9-2 that the available data didn’t show MDMA was effective in treating PTSD, and 10-1 that the benefits of MDMA-assisted therapy did not outweigh the risks.
The panel cited a number of issues around the credibility of the data and research practices, which were also addressed in a paper published by the non-profit Institute for Clinical and Economic Review (ICER) in March. The report highlighted “substantial concerns about the validity of the results.”
This included the blinding of the study—most patients correctly identified that they had been given MDMA—and “very strong prior beliefs” about the benefits of the treatment among both participants and therapists, which “raise concerns about bias.”
In the days since the decision, many experts have commented that the blinding issues alone should not have been enough to sway the panel.
It is not uncommon for drugs which are easily identifiable in clinical trials, such as those used for sleep and anxiety, to be approved by regulators, explained Matthew Johnson PhD, a scientist at Sheppard Pratt, who has been investigating psychedelic medicines for over 20 years at Johns Hopkins University. He said in an interview over Zoom that he had a sense the treatment may be being “held to a higher standard.”
However, other issues included a lack of diversity in the trials and a failure to provide data on adverse effects such as potential for abuse, with concerns raised that “therapists discouraged reports of substantial harms” and that psychedelics were treated more like “a religious movement” than “pharmaceutical products.”
Sarah McNamee, a Phase 3 trial participant, wrote in a letter to the advisory panel that during her treatment she was encouraged to view her “worsening symptoms as evidence of healing and spiritual awakening.” She says she was repeatedly told she was “helping make history” and was “part of a movement,” and that her responses “during and after the trial could jeopardize legalization.”
Others who gave evidence to the panel raised serious concerns about the conduct of Lykos and its therapy model.
The ICER included public reports of sexual boundaries being “severely crossed” with at least one patient in a Phase I MAPS trial. In 2019, MAPS commented that the two therapists involved, a married couple, had violated ethical standards and had been barred from all MAPS-related activities and from becoming providers of MAPS-affiliated MDMA-assisted therapy should the treatment be approved.
A citizen petition which raised concerns about the MAPS trials, and led to an extension of the public comment session during the hearing, also cited allegations of “entrapment, sexual abuse, and coercive control” connected to the “organizational culture and psycho-spiritual beliefs around ‘healing’ that are encoded in the MAPS/Lykos protocol.”
One of the authors of the petition, Neşe Devenot PhD, a lecturer at Johns Hopkins University who is involved in psychedelic research, referred to Lykos’ research practices as a “therapy cult,” which she expands on in a 17-page document submitted as supporting evidence to the panel.
In a statement following the panel, Devenot said that while she “believed in the therapeutic potential of MDMA” she expressed serious concerns about the organizations’ “dangerous” therapy model, referring to a “wide range of exploitations and abuses.”
In response, Lykos said that as a pharmaceutical company it follows “all industry regulatory requirements,” noting that MAPS is a “separate non-profit entity.”
In line with a Special Protocol Assessment (SPA) Agreement with the FDA, which Lykos say was reached in 2017, sites were “trained to report adverse events per the protocol.”
They added that through an informed consent process “participants were free to discontinue from the studies at any time,” with any reports of misconduct investigated and reported to health authorities.
Russell Hausfeld is a journalist at the psychedelic research nonprofit and media outlet Psymposia, which has spent years investigating the conduct of MAPS and now Lykos. The organisation was the focus of Psymposia’s Power Trip podcast, co-produced with New York Magazine.
In an interview over Zoom, he said that the site has been contacted by a number of whistleblowers and former employees expressing concerns about the company’s conduct.
“After the citizen petition came out, a lot of people reached out to say they had worked with the company and quit because they were worried about their reputation moving forward,” says Hausfeld.
Individuals have spoken about a “sloppy” approach to data and a situation in which “anyone in the company could access and potentially edit” trial results, according to Hausfeld.
Lykos says it “stands by the rigor” of its studies, which were “conducted under guidelines for good clinical practices (GCP), which is monitored, audited, and is further inspected by the FDA as part of the review process.”
An “independent Data Monitoring Committee” is said to have provided oversight for the studies, and the company insists that “clinical site personnel, including therapists, responsible for study conduct decisions, did not have access to the blinded endpoint database.”
Lykos has an “established quality management system to help ensuring participant safety, and data integrity” which includes a “robust audit program to oversee vendors, systems, and investigator sites for compliance to regulations.”
“The database was validated, access permissions were controlled and there are complete audit trails to demonstrate no manipulation of data,” the company says.
But concerns around the safety of patients who are being placed in vulnerable states during psychedelic trials are echoed by others in the field.
The ICER report highlighted how MDMA “breaks down barriers, heightens suggestibility, and creates a substantial risk with any therapists who might choose to take advantage of patients,” while there have been previous reported cases abuse by psychedelic therapists.
“Unfortunately, it’s just not that uncommon in this space for these sorts of loose boundaries to occur,” says Hausfeld, who explained how some therapists in the field feel that touch can be an important part of a person’s psychedelic experience and to deny someone this could be “traumatizing.”
A recent report by STAT highlighted concerns among former Lykos/MAPS employees about the company’s approach to touch, including a training manual that “encouraged physical touch.”
Lykos says that therapeutic touch, such as “hand holding or a hand on their shoulder” was described “to provide guidance to what is appropriate as a part of the Treatment Manual.”
Independent, mental health professionals are also said to have reviewed video recordings for each Phase 3 participant to “assess therapist adherence using 56 criteria for preparatory, experimental, and integrative sessions.”
The company says it “continues to assess practices regarding the safety of patients through a code of ethics, compliance procedures, a robust quality system, ongoing reviews of clinical trial processes, and ongoing risk assessments.”
Meanwhile, Johnson spoke of what he described as an “ego problem” in the field, which he says can stem from the significantly meaningful experiences that people can have whilst taking psychedelics.
“A surprising number of people will say it was the most meaningful thing that’s ever happened to them,” he explains, adding that he fears it could lead to some doctors “acting more like cult leaders.”
This sense that psychedelics are for the “future of humanity” and so the “ends justify the means” can also lead to an “inclination to sweep things under the rug,” he says, or “not ask certain questions or collect certain data” because “we might get an answer that we don’t want” and “we don’t want to give ammunition to critics.”
Johnson, who has published a number of papers on how to safely regulate psychedelic therapies, adds: “We need to see the good, the bad, the ugly, if you want to see this therapy successfully approved… There’s always a risk-benefit ratio.”
The outcome of the FDA panel has left many wondering where the field goes from here.
A final decision on MDMA-assisted therapy will be made by the FDA in August, and although regulators are not bound by the panel’s guidance, sources say it’s unlikely they will go against it.
Lykos remains optimistic, however, saying it will work with the FDA on “how best to support the responsible integration of MDMA-assisted therapy into the healthcare system.”
A spokesperson added: “As the first company to seek approval of MDMA-assisted therapy, we take this responsibility seriously and are working closely with the FDA to ensure that this potential new acute intervention is implemented responsibly and that it is administered to appropriate patients by clinicians who have been trained.”
Hausfeld doubts that a rejection will be the “complete roadblock” for the industry many people believe it will be, but hopes this will at least be a “learning moment.”
“I think moving forward, people are going to be less attached to this ‘movement’-oriented language and we’ll see more picking apart the motives behind this research and those who are conducting it,” he says.
Johnson believes that future investigators may invest in more robust trials, and that having things in place such as REMS [Risk Evaluation and Mitigation Strategies], training programmes and state boards can “minimize” potential concerns and keep things “on track.”
“Support for psychedelic medicine is one of the few bipartisan issues in the U.S… in the scientific community people really want better treatments,” he adds.
“It could really help a lot of people, but on the other hand it’s not going to work for everyone, it’s not going to lead to utopia.”
Meanwhile, the VA plans to conduct and fund further studies on MDMA and other psychedelic compounds “under stringent protocols” to evaluate efficacy and safety and determine how to deliver “maximum benefit to veterans, while minimizing risks.”
Terrence Hayes, VA press secretary, said in a written statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans…. VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”
This article is intended as a piece of objective reporting and doesn’t necessarily represent the views of the author.
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