Varun Saraswathula | Psychedelics are redefining well-being; Penn needs to get involved

In 2016, a group of scientists out of Johns Hopkins University ran what was, at the time, a rather strange clinical trial. They gave doses of psilocybin, the psychoactive component in “magic mushrooms,” to 51 terminally ill cancer patients who underwent two “sessions” (i.e. administrations of the drug guided by a professional) over five weeks with a six-month follow-up. Most of the participants were “psychedelic naive,” or hadn’t used any psychedelic drugs in decades. The investigators were curious as to what psilocybin would do to a group of patients for whom death was on the horizon.

Almost all participants reported substantial reductions in anxiety, depression, and fear of dying almost immediately after administration. Just six months after treatment, 60% of participants experienced a remission in their anxiety and depression symptoms and more than 80% reported feeling an increase in how satisfied they were with life. The Hopkins trial suggests that psilocybin was able to do for cancer patients what many traditional depression treatments have not.

In the past fifteen years, research into psychedelic drugs has boomed. It’s not just Hopkins — effective trials have been held at academic institutions like University of California, Berkeley, New York University, and Mount Sinai School of Medicine, in addition to nonprofits like the Multidisciplinary Association for Psychedelic Studies (MAPS)  and numerous publicly traded companies like Compass Pathways and Atai Life Sciences. Notably, none of this cutting-edge research is happening at Penn — and this is an injustice not just to the field, but to Penn’s role as a leader in mental healthcare.

To be fair, getting approval to run trials with psychedelic substances is incredibly difficult. Under federal law, they are Schedule I drugs, or drugs with “no currently accepted medical use and a high potential for abuse.” This designation is, for the most part, scientifically unsubstantiated. The clinical trials done on psychedelics — most of which are privately or investor funded due to a lack of government grants — have repeatedly shown that the administration of psychedelic substances like psilocybin, MDMA, and LSD in conjunction with psychotherapy is associated with an astonishing relief of psychic pain. Moreover, they do not carry an elevated risk of addiction, unlike some (often widely prescribed) treatments. 

Clinical research on psychedelics began after Dr. Albert Hoffman's discovery of LSD 1938, and the 1950s and 1960s subsequently saw a boom in psychedelic research. However, the association of psychedelics with “hippie” counterculture gave them a bad reputation. In fact, Richard Nixon once referred to Timothy Leary (a Harvard psychologist who championed psychedelics in the 1960s) as “the most dangerous man in America,” and psychedelics — along with any associated research — were completely banned. 

However, the recent growth in the field of psychedelic medicine has seen unprecedented enthusiasm. The companies doing research in this field are making unimaginable amounts of money through investors, and organizations like MAPS often have to turn down donors because they have so much funding. Moreover, psychedelic research is being widely discussed in the media, with a recent New York Times headline proclaiming that “Psychiatry May Never Be the Same.” These drugs have successfully penetrated the zeitgeist in a way that no psychiatric treatment has done since Prozac in the 1980s. But how do these drugs even work?

Psilocybin — along with the other so-called classical psychedelics (LSD, mescaline, and DMT) — works by acting primarily as a 5-HT2A receptor agonist in the brain. In other words, psilocybin molecules bind to certain receptors in the brain that facilitate the release of serotonin, a neurotransmitter that seems to be related to human moods and emotions. These drugs are fairly well-understood in the neurochemical context, but the subjective experiences generated by them are fascinating and mysterious.

“Everything that you see — the colors, the imaginations, the beauty of things, but also the trauma, the fear, the anxiety, the depression, the ego — it's all magnified,” said a College sophomore (who spoke to me on the condition of anonymity) describing his own experiences with LSD. He described seeing visualizations of unimaginable beauty and feeling a oneness and clarity that he never experienced through sobriety. However, he also described a searing and crippling insecurity that made him feel like he was literally dying. 

There’s something that sets apart psychedelics from traditional mental health treatments or even traditional recreational drugs. The goal of psychiatric drugs is to rescue a “normal” phenotype, or in other words, eliminate some sort of pathological trait like depression or anxiety. Alternatively, recreational drugs often seek to augment some desirable feeling (ecstasy, relaxation, excitement, etc.) that humans already experience. Evidence suggests that psychedelics certainly do the former, and during the midst of a “trip,” they also tend to do the latter (without the associated risks of addiction). However, there is a key difference between psychedelics and most other psychoactive chemicals — for the experiencer, psychedelics seem to break reality itself.

The fact that these experiences are modulated by the same serotonin systems as many other traditional treatments makes it even more peculiar. Sure, the antidepressant and anxiolytic properties of psilocybin that the Hopkins study found aren’t necessarily surprising — many effective medications target serotonin. What sets apart psychedelic treatments, as highlighted by the Hopkins study, are the reports of profound and lasting feelings of spirituality. Around 70% of the trial participants found it to be among the top five most meaningful and spiritual experiences in their lifetime. 

But, what does it even mean for an experience to be spiritual? Moreover, how can we study these experiences with the same rigor as other fields of science?

“There's a long history of researching these kinds of experiences going back, at least, to William James,” says Dr. David Yaden, an assistant professor at the Johns Hopkins School of Medicine’s Department of Psychiatry and Behavioral Sciences. “He set the foundation for this kind of research.” 

William James, known as the “father of American psychology,” was a philosopher and psychologist who was one of the first to attempt to study the mind in a systematic and scientific way. He wrote a number of books and theorized principles that are still studied today. Yet, among his most interesting works is "The Varieties of Religious Experience," in which, in his own words, he studied “the feelings, acts, and experiences of individual men in their solitude, so far as they apprehend themselves to stand in relation to whatever they may consider the divine.” 

In other words, James sought to understand what it is that makes an experience “mystical” or “spiritual” and why that even matters, not unlike Dr. Yaden himself. “I did my doctoral work in psychology at Penn, and I was mostly interested in brief experiences that have the potential for long term positive impact,” says Dr. Yaden. While at Penn, he conducted a number of studies trying to more deeply understand the nature of experiences that people classified as “mystical,” “spiritual,” or “self-transcendent.”

There’s no hard and fast definition to what constitutes a mystical experience, but Dr. Yaden suggests that “vastness” — or something that makes the experiencer feel small — is a central part of awe, another type of self-transcendent experience. A classic example is the physical vastness that results from standing in front of the Grand Canyon, seeing a huge building up close, or looking at Earth from orbit. Dr. Yaden adds, however, that “conceptually vast” experiences — like hearing “an idea that has massive implications like... a TED talk that was jaw-dropping” — can be just as profound.

Dr. Yaden studied such experiences retrospectively through the Varieties Corpus, a project he founded in Penn’s psychology department that sought crowd-sourced first-person reports of mystical, spiritual, and self-transcendent experiences. He also tried to induce such experiences non-pharmacologically (that is, without any drugs) and elicit feelings of well-being experimentally, but they didn’t really seem to manifest. “[I tried] non invasive brain stimulation, awe-inspiring videos, virtual reality… as well as meditation, and it seems like psychedelics are really, by far, the most effective means to induce these kinds of experiences.”

So, he moved to Hopkins, where he was a postdoctoral researcher (and later became an assistant professor) at the Center for Psychedelic and Consciousness Research, one of the few academic centers in the United States dedicated to studying the neuropsychiatric impacts of psychedelic drugs. They have done groundbreaking research with psilocybin in treating depression, anxiety, and nicotine addiction, among other pathologies.

The data is undeniable: The therapeutic potential of psychedelics is nothing short of miraculous. These drugs may very well furnish an arsenal of treatments available to mental health providers, who must often resort to using medications that are moderately effective or carry onerous side effects.

However, a more interesting consequence of these treatments to me is that a cultural normalization of psychedelic therapeutics implies a cultural normalization of the spiritual and mystical. Once concepts that were largely limited to religion and fringe neuroscientists, spirituality and mysticism are quickly becoming ideas that are worthy of intellectual curiosity and academic scrutiny. They are changing how we define well-being itself. Repeatedly, clinical trials suggest that the spiritual and mystical experiences occasioned by psychedelics are correlated with a staggering abatement of depression and anxiety, among other illnesses. 

Though there is an ongoing debate between scientists, many (including Dr. Yaden) believe that the subjective experience of psychedelics is needed to facilitate the lasting beneficial impacts seen in clinical trials. But in the context of the psychological and psychiatric establishment, this is foreign and largely uncharted territory. Treatments like psilocybin-assisted psychotherapy have no precedent in modern healthcare, and if they are to be widely disseminated, there needs to be a structural framework for treatments. 

While the current organizations studying psychedelics are often focused on pharmacology and clinical delivery, there are thousands of other questions that span other fields — philosophy, health services research, economics, nursing, law, policy, etc. — that could be studied right here at Penn. Many peer institutions such as Hopkins and NYU have centers for psychedelic research, and by not doing that research here, Penn is falling behind in one of the most interesting and powerful segments of psychiatry and mental health. A Penn Center for Psychedelic Research is poised to approach the field from an interesting perspective — with a top rated nursing school and the Leonard Davis Institute of Health Economics, experts at Penn can study the questions about psychedelics that nobody seems to be answering:

How do we train mental health professionals to correctly guide people in such a vulnerable state? How do we pay these professionals to administer these treatments? How do we measure quality and patient centered outcomes? How do we define scope of practice (i.e. how do we delineate the roles of doctors, nurses, and psychologists) in this space? Importantly, how do we ensure equitability in the availability of these treatments for patients? Should we even limit these treatments to people with mental illness, or should we also allow healthy people a safe, guided psychedelic experience for personal development? 

These questions beget more questions, and it will take years of data collection and analysis to adequately answer them all. Penn can and should be a leader in this field — for the sake of those who are suffering and need these treatments the most. 

VARUN SARASWATHULA is a College senior and first-year Masters in Public Health student from Herndon, Va. studying neuroscience and healthcare management. His email is vsaras@sas.upenn.edu.