At a U.S. Department of Health and Human Services (HHS) workshop about psychedelic medicine earlier this month, the director of mental health for the Department of Veterans Affairs (VA) said she thinks research into psychedelic-assisted therapy needs to more closely resemble real world scenarios. Requiring subjects to have specific diagnoses and pass strict screening protocols, she said, makes it impossible to accurately generalize the effects of such treatment on patients.
“There has been great interest in this,” said Rachel Yehuda, who is also a professor of psychiatry and neurobiology who chairs the psychiatry department at the Icahn School of Medicine at Mount Sinai. “However, one of the things that has been truly disheartening to me is that there’s so many ways to be screened out based on psychological and medical exclusions.”
“Maybe we’re being ultra-conservative, because psychedelics, they still have that taint of being potentially dangerous and Schedule I compounds,” Yehuda continued, “but when we talk about, for example, people of color not being represented, I thought for sure we were going to solve this problem.”
In her own research at a VA facility in New York, for example, only about a third of patients are white, Yehuda said. But because of screening for comorbidities, which are more common in vulnerable populations, many people of color end up being excluded from psychedelic studies. “We have many, many patients who are Latina and African American,” she said, “but because of many health inequities, a lot of them screened out.”
Yehuda was speaking as part of a panel on the “practical aspects of psychedelics research,” one of three sessions at the September 14 HHS workshop called “Exploring the Ethical and Practical Considerations of Psychedelics Research” and hosted by the department’s Office of Human Research Protections. Other sessions focused on ethics and laws around psychedelics, as well as how to safeguard public trust and prevent a “psychedelics bubble.”
“I’m just wondering whether we are designing our trials in a way that is hospitable to all the people that we really want to study so that our results can be generalizable,” Yehuda said during the discussion. “I’m getting emails all the time [from people] who are desperate and tell me their life story,” she said. “By the second paragraph, I know that they’re going to screen out because we’re not taking those complex cases with comorbidities. And I think that’s an ethical issue.”
Yehuda also discussed some of the difficulties around blind studies, in which subjects, and often researchers, are supposed to be ignorant of whether an experimental therapy or a placebo is being used. In the psychedelics space, placebos can be difficult to design because the substances typically produce a noticeable experiential reaction, Yehuda said. On the other hand, she noted that research into psychotherapy techniques typically isn’t designed around blind trials. “The question is, what are we trying to control for in studies that use active placebos?” she asked.
She noted that unlike with some pharmaceutical trials, research into psychedelics has typically paired the experience with some form of more traditional therapy, such as talk therapy. “Nobody—nobody—has done a trial where they’re just giving a psychedelic and then saying, ‘See ya!’ and they’re not doing the adequate preparation, support or integration,” Yehuda said.
Initially, Yehuda said she was skeptical of psychedelics as a tool for mental health treatment, she said. Now she’s more concerned with “what’s the difference between people who respond and don’t respond,” she said.
“An even better question—and this is a study we’re about to undertake—is a dose optimization study,” Yehuda continued, “which asks, ‘Is it really that you’re not a responder, or did you just not get enough of the therapy?'”
A second government official—R. Cameron Wolf, a senior advisor for the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Center for Substance Abuse Protection and the Office of Prevention Innovation—moderated the conference’s third session, which focused on safeguarding public trust in psychedelics and preventing what organizers called “another psychedelics bubble.”
While Wolf primarily asked questions of the panelists, he also observed some similarities between the current psychedelics movement and the circumstances around HIV in the 1980s and ’90s.
“Most of my career has been focused on HIV and scaling up both domestically and internationally programs for prevention, care and treatment, particularly targeted towards key populations and vulnerable populations,” Wolf said, noting “some of the parallels” between that work and the current state of psychedelics.
“There was so much desperation,” he said. “So many people were on death’s door and really looking for answers, looking for treatments, looking for life-saving options, and they were willing to try anything regardless of safety.”
Once more effective medications arrived on the scene beginning in the mid-1990s, Wolf noted, the driving issue changed to one of access. “Even when, in 1996, we had effective combination treatments with protease inhibitors coming out that literally brought people back from the dead,” he explained, “still issues about access and equity—and then how to tailor and target programs towards those most vulnerable—continued.”
“I’ll end by saying this is just the beginning,” Wolf said.
The discussion is unfolding amid an evolving scientific understanding of how psychedelics work and what mental health benefits they might have. The same week as the event, researchers published Phase 3 findings in the journal Nature showing that treatment with MDMA reduced symptoms in patients with moderate to severe PTSD. The findings put MDMA on track for consideration by the Food and Drug Administration (FDA) as soon as next year.
A separate study published last week, meanwhile, found that the use of psilocybin was associated with “persisting reductions” in depression, anxiety, alcohol misuse—as well as increases in emotional regulation, spiritual wellbeing and extraversion.
That followed a separate study from the American Medical Association (AMA) showing that people with major depression experienced “clinically significant sustained reduction” in their symptoms after just one dose of psilocybin.
Another study published last month found that administering a small dose of MDMA along with psilocybin or LSD appears to reduce feelings of discomfort like guilt and fear that are sometimes side effects of consuming so-called magic mushrooms or LSD alone.
A first-of-its-kind analysis released in June offered novel insights into the mechanisms through which psychedelic-assisted therapy appears to help people struggling with alcoholism.
At the federal level, the National Institute on Drug Abuse (NIDA) recently started soliciting proposals for a series of research initiatives meant to explore how psychedelics could be used to treat drug addiction, with plans to provide $1.5 million in funding to support relevant studies.