In 2017, the FDA designated the MDMA-assisted treatment for PTSD as a breakthrough therapy, indicating it may be a significant improvement over existing therapies and clearing the way for further research. The clinical trials tested MDMA in conjunction with intense therapy administered by a pair of therapists to a group of patients with PTSD. In one stage of the trial, 94 patients were given either MDMA or a placebo during three therapy sessions spaced one month apart. Participants also completed integration sessions to help them process their experiences during the drug therapy sessions.

At the end of the trial, 71% of participants in the MDMA group had experienced an improvement in symptoms and no longer met the diagnostic criteria for PTSD. Among the placebo group, 48% of participants had similar results. Some participants in both groups experienced adverse effects such as anxiety or heart palpitations, although none of the adverse effects were characterized as serious. “Consistent with PTSD, suicidal ideation was observed in both groups,” the authors reported in the journal Nature Medicine, “MDMA did not appear to increase this risk, and no suicidal behavior was observed.

” While the research results are promising, an independent investigation of the clinical trial has determined that the findings may not tell the whole story. In a recent draft report, the Institute for Clinical and Economic Review (ICER), a nonprofit that evaluates clinical trials and drug prices, said the investigation found “substantial concerns about the validity of the results” of the MDMA clinical trials. Following the report’s release, a citizen petition filed with the FDA alleged that possible misconduct and ethical violations could mar the credibility of the MDMA research.

The ICER report acknowledges that the research data shows that MDMA may be an “important addition to treatment options for PTSD.” But it also listed several factors that could cloud the results of the study. The report notes that it is not easy to conduct research into psychedelics because it is difficult to obscure which participants are receiving a placebo and which are receiving the active drug because of the unmistakable effects of psychoactive drugs. As a result, most of the study subjects correctly guessed which group they were in, according to a review of the research released by the FDA on Friday.

Without proper blinding, the findings can be skewed by participants or researchers, many of whom see strong promise in the therapeutic potential of the compounds. “There’s the possibility that the data might not be representative of what’s actually happened in clinical trials,” Neşe Devenot, one of the authors of the citizen petition and a senior lecturer in the writing program at Johns Hopkins University who is involved in psychedelic research, told NPR. “I don’t think this has been publicly reckoned with.

” Additionally, the report notes that “very strong prior beliefs” among therapists, researchers and patients influenced the results of the trial. “Concerns have been raised by some that therapists encouraged favorable reports by patients and discouraged negative reports by patients including discouraging reports of substantial harms, potentially biasing the recording of benefits and harms,” the report states. The research was also marred by allegations from a study participant that two therapists– a married couple– engaged in inappropriate physical contact while the subject was under the influence of MDMA during a treatment session in Canada.

An investigation by MAPS determined that the couple had “substantially deviated” from the treatment protocol, leading the organization to notify health authorities in Canada and the United States. Additionally, the therapists were barred from administering MDMA-assisted therapy in affiliation with MAPS. The ICER report has not been finalized, but Dr. David Rind, the chief medical officer for the group says its investigation showed that “there’s still a lot of uncertainty” about using MDMA to treat PTSD.

“You have a group of people who are very upset about how these trials went,” he said. “We couldn’t tell, even though we talked with people where this happened, whether that represents a tiny fraction of bad events or a number of bad events large enough to have rendered the trial just not believable.” Investigators involved in the research, however, have rejected claims that the study is flawed. Jennifer Mitchell, lead author of the published papers from the Phase 3 trials, says she stands behind the study’s findings.

“I didn’t feel any pressure from the sponsor to come up with anything different than what the data was providing,” said Mitchell, a professor of neurology and psychiatry at the University of California, San Francisco and associate chief of staff for research at the San Francisco VA Medical Center. “I wouldn’t have continued to work with them if I had felt that.” The FDA review also expressed concerns about the safety of MDMA, including the risk of abuse and possible side effects that could harm the cardiovascular system and the liver.

Lykos CEO Amy Emerson said the company stands by the quality and integrity of its research and development process.  “Given there has not been a new PTSD medication approved in the United States in over two decades for the 13 million people living with PTSD, we are deeply committed to making a difference by bringing a potential new treatment to patients,” she said in a statement cited by the Washington Post. Shawn Hauser, a partner at the cannabis and psychedelics law firm Vicente LLP, said it is not surprising that the FDA’s consideration of new MDMA-assisted therapies is raising questions, noting that the use of a psychedelic drug in conjunction with therapy is uncharted territory for the agency.

The FDA drug evaluation process is difficult to apply to certain substances and treatments including psychedelics and other compounds including botanical cannabis, although for different reasons. “The promising research makes clear the potential of this therapy for treating PTSD, and while there are certainly challenges in these studies (as with any study) and legitimate concerns that must be addressed, these must be considered in the broader context of the severe unmet treatment needs by patients with PTSD and the strong data on safety and efficacy,” Hauser wrote in an email to High Times.

“The questions around this process clearly underscore that the FDA evaluation process requires modernization to appropriately evaluate treatments like MDMA-assisted therapy and substances like botanical and natural medicines.” Read less