The inside story of how Lykos’ MDMA research went awry

The inside story of how Lykos’ MDMA research went awry

At a heated advisory committee meeting convened by the Food and Drug Administration last week, regulators
repeatedly expressed frustration that Lykos, a company seeking approval of MDMA-assisted therapy to treat
PTSD, failed to follow instructions and track positive feelings such as “euphoria” that could be used to inform
understanding of the drug’s addiction potential.

The missing data, said clinical reviewer David Millis, were “a major concern.”
Lykos executives said they’d simply misunderstood the FDA’s instructions, but three former employees told a
different story. The company was long aware it was required to collect such data, they said, and simply failed to
do what was needed amid widespread disorganization. Employees described waiting in vain for a protocol to
collect the data to be approved, while executives seemed distracted dealing with other problems.

The lapses were part of a pattern of failings at Lykos, according to several former employees, who described a
culture in which complaints were often ignored, and hype around MDMA interfered with a rigorous scientific
process.

Christina Faulk, a former data management associate at Lykos, said she was “relieved” the FDA advisory
committee asked so many questions about patient safety and data integrity. “I had similar questions and concerns during my employment that I felt were not resolved before my departure,” she added. Another former employee,
research scientist Emmett Henderson, said he too shared concerns expressed by the advisory committee panel.
“I’m not surprised most voted ‘no’ and I think that was the right call,” said Henderson.

In a statement to STAT, Lykos said that the company stands by the rigor of its studies and that accusations of
activist hype and dismissal of concerns were unfounded. “The studies were conducted with the appropriate
checks and balances in place,” spokesperson Caroline Rigdon wrote in an email. “Any reports of misconduct are
investigated and addressed as appropriate.” Although the company did not collect data on so-called “positive
adverse events,” like euphoria, for the Phase 3 studies, it did add such data to subsequent protocols, Rigdon said.
Ahead of last week’s meeting, there was mounting excitement about MDMA’s forthcoming review. Lykos
sponsored two successful Phase 3 trials, both with research protocols overseen by the FDA, and researchers were
optimistic that the drug would be the first Schedule I psychedelic to get approval by the FDA come August. That
hope largely fizzled last week, as advisory committee members asked question after question, often scrutinizing
the conduct of Lykos researchers and therapists, rather than MDMA itself.

Lykos, previously known as MAPS PBC (public benefit corporation), was originally formed as a subsidiary of
the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit led by drug activist Rick Doblin
for close to 40 years. The organization was formed in 1986 shortly after the use of MDMA was first criminalized,
and Doblin, who has advocated for world leaders to take MDMA to help further peace talks, was outspoken about
his plans to use research as a pathway to wider psychedelic approval.

These activist origins have been hard to shake, according to interviews with more than half a dozen former
MAPS and Lykos employees, some of whom spoke on condition of anonymity. Although Doblin stepped down as
MAPS executive director last year, he’s stayed on as president of the organization and part of Lykos’s board of
directors. And while Lykos has attempted to distinguish itself from MAPS, former employees say those roots
infiltrated and interfered with scientific research. “The more we tried to make it a scientific company, the more
we got disparaged by the cult side,” said one former Lykos employee. Amid an evangelist culture, several former
Lykos employees voiced concerns about inappropriate access to trial data and a willingness to gloss over
concerns, including one instance of potential trial misconduct.

In a statement to STAT, MAPS said that the organization has “no comment on hearsay” and that Lykos is “fully
and solely responsible” for drug development. “MAPS is an organization with a multi-pronged approach to social
change. It is inherent to such efforts that differences of opinion are welcome, so we embrace differences of
opinion as a critical part of developing and evolving strategies to achieve the mission,” spokesperson Betty
Aldworth added in an email.

The enthusiasm of both MAPS and Doblin helped MDMA advance to the forefront of psychedelic research.
Having got so close, said former employees, those same characteristics then undermined the professionalism.
“I don’t think Lykos likes to be associated with those early stories,” said Jerry Rosenbaum, director of the Center
for the Neuroscience of Psychedelics at Massachusetts General Hospital, who spoke about the clinical need for a
new PTSD treatment at the advisory committee meeting. “As first movers, they had to be exemplary.”

he evangelist attitude of MDMA researchers was repeatedly criticized both during a public hearing portion of
the advisory committee meeting and in a report issued by the Institute for Clinical and Economic Review (ICER),
a think tank, ahead of the meeting. Psychedelics were treated more like “a religious movement than like
pharmaceutical products,” read the ICER report. Researchers told a Phase 3 trial participant Sarah McNamee she
was “helping make history” and was “part of a movement,” she wrote in a public letter to the advisory committee.

This attitude was rooted in MAPS’s fervent activism, said three former MAPS employees. “‘We already know it
works, we just need to prove it in some way’ — that’s a common sentiment in the community,” Ifetayo Harvey,
founder of the POC Psychedelic Collective, who previously worked at MAPS as Rick Doblin’s assistant, told
STAT. “There’s a part of MAPS that relies on new age spirituality and the hype machine.” Another former
employee, who was a member of a cult in her twenties, said there were cult-like tendencies at MAPS:
“Psychedelics lead to that because it’s messianic,” she said.

Deep-seated enthusiasm spurred Doblin through four decades of advocacy. Efforts to stop the criminalization of
MDMA in the ’80s was “almost single-handedly orchestrated, promoted, and financed by a 31-year-old
University of South Florida undergraduate named Rick Doblin,” New York Magazine reported in 1985. When
this initial effort failed, Doblin got his public policy doctorate at Harvard University’s Kennedy School, and
decided to work toward legalization by proving the medical benefits of MDMA. Although MAPS’ research
focused on the drug as a treatment for post-traumatic stress disorder, Doblin’s goals were loftier, heralding “net
zero trauma” and “a more spiritualized humanity.”

Three former employees said excitement around MDMA often led criticisms to be dismissed as evidence of
stigma or prohibitionist tendencies. “I think a lot of the psychedelics world is like that where people have an
underlying sense that psychedelics are this inherent good for humanity and anything you can do to bring
psychedelics to the world is beneficial,” said former MAPS communications director Jag Davies.
Concerns about lack of diversity in clinical trials, and sexual abuse by therapists involved in the administration of
psychedelics — both problems that were raised during the advisory committee meeting — were similarly
overlooked, former employees said. “If people engaged in good faith rather than shutting people down, they
could have had a chance to re-assess their work before going into Phase 3 and improve their science,” said
Harvey. “These critiques have been happening for years now.”

Doblin and MAPS were successful at pushing boundaries for decades, said another former employee. But that
doesn’t necessarily make the organization well-suited for above-ground research. “You can see that historically in
movements. Folks who lead underground, are not necessarily the same as who will lead legally,” she said.
n recent years, MAPS executives realized they needed to disentangle the scientific research from more activist
tendencies and worked to separate MAPS PBC, now known as Lykos Therapeutics, from the wider organization.
The company hired several employees from more conventional research backgrounds, including Michael
Mullette, who came from Moderna to be chief operating officer, to help ensure the research went smoothly.
Jennifer Mitchell, a neurology professor at the University of California, San Francisco, who led the Phase 3
MDMA studies, said she only agreed to do so thanks to these new boundaries. “I do think [Doblin] has an
agenda,” she said. “I was concerned that agenda could impact the science.”

Former Lykos employees said that activist tendencies continued to shape the company’s culture. “There was a lot
of tension between the people who were there for more emotional reasons versus more science reasons,” said one.
The “old guard” similarly seemed uncomfortable in the more “cold and corporate” environment, said another,
who also described “cult-like dynamics,” at Lykos.

Several Lykos’ employees were skeptical about the company’s approach to therapy, including a MAPS training
manual that encouraged physical touch. Those who tried to push back were often cut out of decision-making, said
a former employee: “I was like, we need to button this up.... Why hire us for our expertise?”

Two former employees said Lykos also had an unprofessional approach to data, where nearly everyone in the
company had access to results coming in from the trials. They described how one executive, director of clinical
operations Charlotte Harrison, would periodically download the data to create her own rudimentary graphs,
which she broadcast internally to others at Lykos as evidence that MDMA was performing well, helping to fuel a
heightened sense of confidence.

“I saw MAPS and Lykos get ahead of themselves.... If you raised concerns, they weren’t taken seriously because
everything just seemed to be going well,” said a former Lykos employee.

Trial sites did not have the same open access to data, said Mitchell, who added that data were always locked on
her end. “I don’t know what to say about anyone on the Lykos side taking a peek,” she said.
Lykos denied the claims Harrison downloaded data, saying they were “unfounded” and the company had
“appropriate controls in place with the clinical data.”

A similar lack of professionalism and rigor contributed to Lykos’ failure to collect data on positive adverse events
that were requested to help inform data on MDMA’s addiction potential. “They simply didn’t do it. People argued
about it round and round at the company,” said one former employee, who said they were denied the chance to
see what the FDA had requested. Mitchell, the researcher who ran the Phase 3 trials, said Lykos never told her of
the need to collect this data, even when her team explicitly asked if they needed to record positive events. “We
were very surprised to hear all of this [the FDA’s request],” she said.

Concerns about disorganization and lack of rigor were often dismissed, said former Lykos employees. On one
occasion, a trial participant hadn’t completed a questionnaire and, without the full set, none of the data could be
entered into the system. Lykos researchers suggested entering a value, and simply noting that one of the numbers
was entered at random. The plan reflected a lack of competence rather than an intentional desire to skew results,
said three former employees with knowledge of the event, but was still inappropriate, as the random value would
distort evidence.

A colleague who warned this was trial misconduct and tried to file a complaint was then shut out of the
discussion and wasn’t told of how their concerns were resolved, said three former employees. Lykos investigated
and addressed reports of misconduct “as appropriate,” Rigdon wrote to STAT.

Issues over rigor and culture weren’t the only problems. Members of the advisory committee also expressed
concern about the lack of “functional blinding” — that is, both patients and likely therapists knew who received
MDMA as opposed to placebo — and the difficulty in disentangling the effects of the drug from the therapy. Both
those problems are inherent to psychedelic research and trial designs that had already been approved by the FDA.
As the first Schedule I psychedelic to go up for FDA review, MDMA faced more intense scrutiny than most
drugs, said both Rosenbaum and Mitchell. Rosenbaum said he felt many of the concerns could be addressed
through post-approval research, and Mitchell said she’s repeatedly asked for federal funding for a study that
would include arms focused on MDMA alone and therapy alone, but has been denied the funds.

Although the advisory committee didn’t hear directly from former Lykos employees, the conversation at the
hearing reflected shared concerns about Lykos’ research lapses. “It seems like there are so many problems with
the data. Each one alone might be OK,” said Melissa Barone, a staff psychologist for the VA Maryland Health
Care System Trauma Recovery Program and member of the advisory committee. “But when you pile them on top
of each other...there’s just a lot of questions I would have about how effective the treatment is.”
Questions about how Lykos responded to criticism also shaped the discussion, with UCLA psychiatrist and
advisory committee member Walter Dunn asking Lykos executives if the company investigated concerns laid out
in the ICER report. At the meeting, senior medical director Alia Lilienstein said the allegations were investigated,
but didn’t provide any detail. In a later interview with STAT, lead trial investigator Mitchell said she thought it
was a “very good” question, but had “no idea” if the allegations were investigated. Lykos told STAT a third-party
law firm carried out the investigation.

Even while voicing critiques, both former MAPS and Lykos employees said they believed MDMA therapy could
ultimately be beneficial. Veterans make up a large proportion of trial participants, and several former service
members spoke at the advisory committee’s public hearing about the treatment’s ability to ease trauma. Faulk,
who is also a Navy veteran, said she “firmly” believes in the potential of psychedelics as medical treatment, and
hopes to see more funding for research. Only those studies should be at a higher standard, she added: “It is
imperative that we approach their integration into clinical practice with caution and diligence, ensuring that
rigorous standards are upheld at every stage.”