The journal Psychopharmacology has retracted three papers about MDMA-assisted psychotherapy — right on the heels of the Food and Drug Administration’s rejection of the closely watched treatment for post-traumatic stress disorder.
Many authors on the three studies are affiliated with the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS) and its commercial spinout Lykos Therapeutics, including founder Rick Doblin, who spearheaded the decades-long efforts to win approval for the psychedelic treatment. Lykos CEO Amy Emerson is an author as well.
The retractions were due to “protocol violations amounting to unethical conduct,” particularly during a Phase 2 trial at the MP4 study site in Canada, Psychopharmacology said. This site is where an unlicensed therapist was accused of sexual assault in civil court by a MAPS trial participant.
The authors of the papers, published in 2020 and 2021, confirmed they knew some of the data were linked to ethical violations when they submitted the papers, the Psychopharmacology retraction noted. But they didn’t disclose that to the journal or remove data from the site from their analysis.
“This is a forceful message that psychedelic research will and should be held to a high standard of ethics and accountability,” said Boris Heifets, a neuroscience researcher at Stanford University who studies psychedelics.
Issues with data integrity and research bias have been an ongoing concern during Lykos’ ill-fated bid to win approval for MDMA-assisted therapy. In March, the Institute for Clinical and Economic Review think tank published a report that raised questions about whether participants’ serious adverse events, including extreme mental distress, were accurately reflected in the research data.
Activist groups have also been clamoring for regulators and academics alike to further scrutinize the reliability of Lykos’ data, in part due to reports of suicidality and assault among a small number of trial participants. On Friday, the FDA said Lykos needed to conduct another Phase 3 trial to further study the drug’s safety and efficacy if it wanted to ultimately win approval.
Doblin and some other authors disagreed with the retraction, saying instead that a correction would have sufficed. “The authors are actively working to correct all publications including these data with the appropriate disclosures to best preserve the integrity of the scholarly record,” Lykos said in a statement.
Lykos said it has filed an official complaint with the Committee on Publication Ethics to review how Psychopharmacology came to this decision. Lykos also said that it did report the ethical violations to the FDA, Health Canada, and the Institutional Review Board and Independent Ethics Committee, and issued a public statement about it in 2019.
“However, we did not disclose the violations to the journal itself, an additional step we should have taken and regret not doing,” Lykos said.
The company said that Psychopharmacology had initially requested that Lykos make a correction — so “the authors removed the data from the four participants treated in the MP4 study, and the updated analyses were consistent with the original publications.” The four participants were at the MP4 site, which was led by the therapist accused of assault in the civil case as well as his wife.
The retraction notice also says that the authors did not fully declare a potential competing interest. Lykos disagreed, saying that the authors disclosed all relevant information.
Allison Feduccia, one of the authors in all three studies, said that she agreed with the retractions. Psychopharmacology, she said, would not let the authors amend the data.
“Since a correction was not possible, I agree with the retraction since a participant’s data who experienced an ethical violation was included,” she told STAT in an email.
Sasha Sisko, an activist who has investigated trial conduct at MAPS and Lykos, said that they have been in regular contact with the editor of Psychopharmacology for more than a year sharing information about the ethical violations, including sharing video of the assault at the MP4 trial site.
The data in these studies are not the same as the Phase 3 efficacy data submitted to the FDA that underpinned the treatment’s rejection. One was a pooled analysis of the long-term outcomes from six Phase 2 trials that evaluated MDMA-assisted psychotherapy for PTSD; another outlined the design and rationale for the subsequent Phase 3 studies; the third evaluated how discontinuing the use of certain psychiatric medications impacted the treatment response of MDMA-assisted psychotherapy.
Earlier this year, it seemed inevitable the FDA would approve the treatment: Two trials showed that MDMA-assisted psychotherapy was effective treatment for PTSD, and Lykos also received “special protocol assessment,” meaning the FDA signed off on the trial design. And there’s a tremendous unmet need: There hasn’t been an approved new treatment for PTSD in two decades.
But sentiment shifted in the wake of the ICER report and as trial participants and former employees warned of a cult-like atmosphere within the organization, and excessive hype around MDMA that undermines the results.
“Psychedelics may indeed hold great promise for healing and transformation, and current psychopharmacology falls far short of the mental health burdens we are facing,” said Lori Bruce, associate director of the Center for Bioethics at Yale University. “But aspects of the MDMA research environment have failed to uphold ethical standards.”
Despite having signed off on trial design, FDA regulators also expressed frustration that Lykos had failed to collect data on positive reactions to MDMA, such as feelings of euphoria, which could be used to inform understanding of addiction potential.
Since a contentious FDA advisory committee in June, which overwhelmingly voted against approving MDMA-assisted psychotherapy, several former Lykos employees told STAT the company failed to collect the required data because of disorganization. They also described excessive hype internally, and lack of rigor in the conduct of the trials that included executives looking at trial data while the research was ongoing.
“If you’re telling your investigators not to report negative outcomes, that’s a real cardinal sin against smart drug regulation,” said Peter Pitts, a former associate commissioner for external relations at the FDA. “At Lykos, they’re as much scientists as they are true believers and that’s dangerous, because when you accept fiddling around with data to prove what you know is right, that’s not smart.”
Olivia Goldhill contributed to this story.