Trials looking at MDMA’s health benefits ignored patients’ worsening suicidal tendencies, according to several people involved in the studies.
Three volunteers with PTSD said they felt more depressed in the weeks after the trial began and in the weeks after it ended, an effect of taking the psychoactive drug, also known as “molly.”
Lykos Therapeutics, the company that masterminded the push to legalize MDMA for PTSD, is accused of bias in reporting trial results to show a positive effect on people’s PTSD symptoms, pressuring people to report positive effects, and ignoring those who said their symptoms worsened.
The ongoing trials have been plagued by allegations of sexual misconduct and of doctors overseeing the study holding “clandestine” MDMA sessions not authorized by the trial and using the drugs illegally.
Patients take a dose of the drug under supervision. Sessions with a therapist help people come to terms with their trauma.
MDMA increases levels of three feel-good neurotransmitters in the brain: serotonin, dopamine and norepinephrine. When a person comes down from the drug’s euphoria, levels of these neurotransmitters plummet, leading to depression and anxiety.
The accounts of people’s negative experiences with the drug in a therapeutic setting come amid the FDA’s deliberation over whether to approve a version of the drug to treat post-traumatic stress disorder (PTSD).
The agency’s panel of independent drug reviewers voted overwhelmingly in June against approving it, alleging that Lykos Therapeutics, the company behind this particular formula, suppressed data that researchers did not want highlighted, as well as studying misconduct, including sexual assault.
They also noted that blinding was difficult, since people taking the drug, as well as therapists overseeing their experience, could say they were taking it, while those given placebo could say they were not.
Despite the panel’s recommendation against approval, the FDA does not necessarily have to follow suit and will make a decision by August 11.
The decision will indicate whether the stories of trial participants and their mental health problems are compelling enough to warrant concern.
One of the people interviewed, Sarah McNamee from Montreal, told the Wall Street Journal who felt pressured to report positive results.
She said: “I wanted the miracle cure. My therapists made it very clear to me that they truly believed in this.
“It made me feel like I belonged to something bigger than myself, and it also made me feel like I had a huge responsibility to make sure other people could have access.”
Therapy had made her feel like she had been cut open. The design of the trial was to focus on a traumatic event in her life to improve it, but several traumatic events have affected her.
While she fared better in coping with one of those events, the drug trial brought back painful memories of others.
In a written public comment to the FDA, Ms. McNamee said she agreed to some of the suspicious things the trial therapists did because she trusted them to conduct research that would pass scientific muster.
They also implied that her participation in the trial, specifically if she responded well to it, would lead to a “paradigm-changing treatment.”
She said therapists encouraged her to view her worsening PTSD symptoms “as evidence of healing and ‘spiritual awakening’; sowing distrust in conventional psychiatry; telling me about past-life traumas; encouraging and, once, pressuring me to embrace them.”
She added that when she tried to tell therapists during the rehearsal that she seemed in a bad way, one of them told her that “she would feel better in six months.”
“When I tried to tell my therapists about my emerging and worsening mental health symptoms at the end of the trial, one of them responded that he predicted I would feel better in six months.”
Two other study subjects said they had suicidal thoughts more frequently after the trial ended. At that point, researchers were no longer taking information from the patients and therefore did not take into account that those patients were having an extremely negative reaction to the drug.
One subject refused to participate in a longer-term trial because of the severe toll the drug had taken on his mental health, while the other who did participate in the longer trial said he did not report becoming more suicidal after the initial trial had ended.
They cited biases in the trial design, noting that all of the doctors overseeing the treatments were fervent believers in the drug’s ability to change lives and convinced participants of that, too.
People familiar with the trials also said researchers offered people MDMA for clandestine, unauthorized sessions even while they were participating in clinical trials.
Lykos, however, admits that his investigators pass a serious test to be involved in the trials.
At the same time, the company had to admit that some of its therapists had committed malpractice after one of the study participants reported that both her male and female therapists hugged her tightly while they were lying together in a bed.
Dr. David Rind, medical director of the Institute for Clinical and Economic Review, a nonprofit that analyzes drugs and their pricing, said: “You have to make sure that therapists are very, very clear that they should not imply to people that the trial results are of global importance and encourage people to have favorable outcomes.”
At first, Ms. McNamee believed strongly in the power of psychedelics for people like herself and those suffering from severe depression.
But she said National Public Radio‘Three months after I was given my first dose of MDMA, I was for a time one of the staunchest advocates of MDMA therapy. The problem was that I also had suicidal tendencies and a drastic and unprecedented clinical decompensation.’
Proponents of MDMA for post-traumatic stress disorder (PTSD) are lobbying hard for its approval.
One of MDMA’s most outspoken advocates is retired three-star Marine Corps helicopter pilot Jack Bergman, who is running for his fourth term representing a northern Michigan district in Congress.
He is a Republican and is now lobbying hard alongside other veterans and members of Congress to get FDA approval.
He is joined by other lawmakers, both Republican and Democrat, as well as tech giant Elon Musk.
Bergman saying“Every day that goes by without investigations, more lives are lost, mostly to suicide. Many of these veterans are on a dark path,” he said, and made a gesture of putting a gun to his head.
‘The strategy here is to exert positive pressure so that the bureaucracy feels that it is okay to take some risk.’
In addition to voting nine to two on whether the evidence for Lykos was strong enough to support the treatment’s efficacy, the committee voted 10 to 1 to say the drug’s drawbacks outweighed its benefits.
Some of the risks they cited included possible effects on heart health, potential for abuse, and the fact that Lykos appeared to have omitted important safety results, with one saying: “There are significant gaps in the data.”
MDMA provides an immediate pleasurable feeling by stimulating the release of neurotransmitters, such as dopamine, norepinephrine and serotonin, in the brain.
It is a combination of psychedelic and stimulant and often causes an explosion of energy as well as hallucinations.
Like many addictive drugs, MDMA causes a feeling of euphoria, but is often associated with its social effects, which make a person feel friendlier and closer to other people, and more affectionate. It is most common at music festivals and raves.
A 2014 study shows that MDMA reduced people’s ability to detect anger in others’ faces, but did not affect their ability to identify happy faces, suggesting that the drug’s “prosocial behavioral effects might be partially explained by a reduced ability to perceive negative emotional states in others.”
But it is not without significant drawbacks, including suicidal ideation and tendencies.
Drug use alters a person’s brain chemistry. It can cause anxiety, increased depression and panic attacks, as well as nausea, diarrhea, headaches and insomnia.
It is thought to be due to the rush of feel-good neurochemicals that flood the brain during the high, followed by lower-than-average levels of those chemicals in the hours and days after the drug leaves the body.
This feeling can also encourage the person to use the drug again and continue taking it to mitigate those effects. In 2022, it was estimated that around 2.1 million people in the United States had used ecstasy, also known as MDMA or Molly, in the past year.