Are psychedelic drugs about to begin a long, strange trip toward use in a clinical setting? Or do the challenges of studying psychedelics, and the ethical risks of therapy, raise too many questions to introduce them into mainstream medicine?
As debate continues if—and how—psychedelics should be used, a Food and Drug Administration advisory committee recently voted down a proposal brought by a drugmaker to use MDMA to treat post-traumatic stress disorder (PTSD), in combination with talk therapy. The committee recognized the promise of psychedelics but raised serious concerns about the science and the ethics of psychedelic treatments.
The vote came before the full FDA decided not to approve the drugmaker’s application, asking the company to conduct additional study on the safety and efficacy of the treatment. However, the decision doesn’t completely close the door and the FDA can still eventually approve other applications. If so, there is a growing movement of cross disciplinary experts crafting guardrails for how psychedelic drugs should be used.
Dominic Sisti, PhD, an associate professor of Medical Ethics & Health Policy in the Perelman School of Medicine at the University of Pennsylvania, was part of a group of nearly 30 experts including bioethicists, psychiatrists, Indigenous scholars, researchers, and others to begin charting a path toward crafting guidelines for the ethical use of psychedelics. The group’s work was published in JAMA Network Open, setting the stage for the next phase of psychedelics in psychiatry.
The paper is the result of a workshop held at the Banbury Center of Cold Spring Harbor Laboratory and funded by the Project on Psychedelics Law and Regulation (POPLAR) at the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School. The meeting was organized by researchers from the Center for Medical Ethics and Health Policy at Baylor, Petrie-Flom Center, Harvard Law School and the University of Pennsylvania Perelman School of Medicine.
Sisti described the group’s work as “an inauguration of a new area of bioethics.”
“Bringing together this many stakeholders for the first time really helped to kick off a concerted effort by bioethicists to study psychedelics and their role in health care,” he said. “The bioethical issues that accompany psychedelic-assisted therapy have been discussed over the years, but not in a systematic way.”
Recognizing history & equity
Psychedelics is an umbrella term often used to describe drugs, either natural or manufactured, that provide mind-altering effects.
MDMA—commonly referred to as ecstasy or molly—is a lab-made drug with properties similar to stimulants that also distort a person’s sense of time, and can give feelings of closeness, empathy and reduce inhibitions.
Psylocibin is a chemical found in certain types of mushrooms (hence the name association with “magic mushrooms”) with a history that stretches back millennia. These can also alter a person’s sense of sight and sound, while imparting a wide range of emotions.
Though popular culture often depicts psychedelic drug use as a product of 1960s counterculture, mind-altering drugs have been used by humans in some form for millennia. In 2008, archeologists at a 1,000-year-old site in Bolivia discovered psychoactive botanical substances found in a hallucinogenic cocktail known as ayahuasca.
According to Sisti, recognizing history like this was a central theme of his group’s work examining the potential for psychedelic use in modern medicine.
“Just imagining that if psilocybin is commercialized—should shamans in Mexico and Central America, where some of these medicines originated, receive some sort of direct benefit from the research?” Sisti said. “It’s an issue at the intersection of ethnobotany, colonialism, research ethics, reciprocity, and respect.”
Another aim was to refresh current approaches, such as informed consent: straightforward communication between a patient and their healthcare provider to achieve a shared understanding of care.
In other words, how can a provider fully prepare a patient for a psychedelic experience that can’t really be imagined before it is experienced?
“When you think about it, we take big risks in our life without knowing or imagining what the outcome is going to be,” Sisti said. “Having kids, getting married, pursuing various hobbies—these are things that we do with a sort of foresight that we think will be good but we’re not totally sure what the experience is like at all. It’s almost a similar leap of faith in that way.”
Sisti also noted the importance of establishing equity, particularly through potential clinical trials that have not historically been diverse in representation.
“One of the issues to solve for is instilling trust in the Black community, that has been criminalized for using drugs like cannabis, to participate in trials,” Sisti said.
Widening the treatment lens
Currently, some cancer patients have accessed these medicines in limited clinical trials. Kayla Baker, MBE, MSN, CRNP, RN, was an oncology nurse before becoming a PhD candidate at Penn Nursing in a dual degree program which includes a Master’s in Bioethics at Penn. She is also drawing on her background and experiences to pursue research in this arena.
“I had the opportunity to talk to people with cancer and depression who participated in a clinical trial of psilocybin-assisted group therapy,” Baker said. “I noticed that the therapy seems to highlight the ability to access some of the more spiritual and existential concerns that people have, that are often difficult to address in the medical context. Psilocybin often causes people to have ‘mystical experiences,’ which is a well-documented phenomenon.”
Baker also noted that those interviewed reported how the treatment changed their perspective, leaving them more accepting of themselves and others.
“They are more at peace with the challenges of their illness and difficult questions about illness, life, and death,” she said. These are often questions that, Baker noted, medical professionals may not feel equipped to address.
“My research has shown me that for patients that are able to face these issues with psilocybin-assisted therapy, it can be extraordinarily healing,” Baker said. “I do not want to overstate the benefits, but I can think of so many patients I have cared for over the years who may have benefitted from this therapy, and I am hopeful that the research so far shows it is largely safe and effective when delivered in a supportive therapeutic environment. We still have a lot of research to do, but I think this is going to be a pivotal new therapy.”
The next frontier for psychedelics in medical care
So, what happens now?
Assistant Professor of Psychiatry Emily Hartwell, PhD, a substance use researcher who was not involved in this work, echoed the practical importance of proactively creating guidelines and creating a “solid scientific base” before approaching things like dosing, scheduling, and therapy.
“That is a piece that can be left out of these conversations,” Hartwell said. “Typically, what we see in trials is that people that react the best take the drug in combination with therapy,” such as how some patients take selective serotonin reuptake inhibitors (SSRI) in combination with psychotherapy for treating depression.
Accessibility is another point Hartwell emphasized: If a new treatment option is authorized, it should be widely available and priced affordably.
“From a substance use perspective, my other concern is that it wouldn’t be available to your average person who has treatment-resistant depression, who could really benefit from this and who's tried every other thing under the sun,” Hartwell said. “They may be priced out of this as an option.”
The committee considered an application from Lykos Therapeutics seeking approval of MDMA for treatment of post-traumatic stress disorder. Most committee members were unconvinced that this company’s clinical trial data adequately demonstrated the drug’s effectiveness; they were also unconvinced that the drug’s benefits would outweigh the risks, even with additional safeguards around use.
“The FDA is not legally bound to follow the committee’s votes,” said Holly Fernandez Lynch, JD, ME, assistant professor of Medical Ethics and Health Policy, “although they usually do.” That would represent a setback for psychedelic drug development but, Fernandez Lynch added, many of the concerns were specific to this particular application.
“The FDA will want to get the first psychedelic drug approval right. The committee’s concerns, which echoed several concerns raised by FDA scientists, offer clear guidance to drug developers about what will be expected in this space,” she said. “This is doable.”
Still, while the path from guidelines to implementation may be a long one, those first steps are important. Sisti struck a similarly cautiously optimistic tone on the future of psychedelics in health care, noting also that they should be part of a broader spectrum of treatment.
“The medicines, themselves, can help with treatment but also help us understand the brain and how to pursue treatment through new mechanisms,” Sisti said. “It’s exciting that we’ve taken the first steps to put an infrastructure together for that work.”