Experiencing Psychedelic Clinical Trials from a Participant’s Perspective

Psychedelics as a class are not just another study drug. They have recently drawn intense scrutiny for being potentially effective in treating serious mental health conditions that lack good treatment options. However, they have a host of unique associations and face immense obstacles to achieving regulatory approval. They are classified as Schedule I drugs, without current accepted medical use and with high abuse potential. Further complicating matters, psychedelic compounds may not have similar effects or side effects even if they have a similar structure or produce a similar subjective experience. Taking a closer look at the participant experience in a clinical study with a psychedelic can help the research community understand the journey, and how to help the journey be the best it can.

Public Opinion

The general population is somewhat aware of psychedelics and has already established opinions about them. A U.S. survey of 1,800 adults in 2022 showed that only 15% of respondents had a positive attitude toward psychedelics. Of that 15%, only 24% were in favor of using psychedelics for mental health conditions, although that number rose to 36% if they had seen a therapist recently. Another U.S. survey of 1,500 adults conducted one year later revealed that 61% of respondents supported legalizing regulated therapeutic access to psychedelics with 35% expressing strong support. However, 61% of that sample thought that psychedelics were not good for society and 69% said that those drugs were not for someone like me.

Clinical Research

If that is public opinion, what does data from clinical research into common and serious mental health conditions such as depression, anxiety, and post-traumatic stress disorder (PTSD) show? Systematic reviews conducted from 2018 to 2022 of psilocybin, LSD, and ayahuasca clinical trials, to pick three of the many products being studied, showed strong evidence of improvement in generalized anxiety disorder, alcohol dependence, major depressive disorder including treatment-resistant depression, and cancer-related anxiety. These included studies of varying quality, and a growing body of well-designed clinical trials. These effects included results from single treatments, with immediate, significant and enduring effects. Of note, the studies also showed these treatments to be feasible and with limited side effects. Moreover, the rate and pace of clinical trials in psychedelics has increased exponentially, from fewer than 50 published articles in 1990 to more than 700 in 2020.

Most importantly, these products are showing promise for significant diseases without good treatment pathways. Two examples are major depressive disorder (MDD) and PTSD. From a simplistic economic viewpoint, MDD has an annual $93 billion impact on U.S. health and society with about $44 billion of that being treatment resistant disease. PTSD has a staggering and underappreciated social and economic impact of about $232 billion per year.

While some researchers are going through the required clinical trials to develop an FDA-approved medicine, other avenues are also being taken, including several U.S. states introducing their own measures. For example, Oregon’s Psilocybin Services Act requires a trained and licensed facilitator to administer psilocybin at a state facility and does not specify the purpose of the use. Two of Utah’s largest healthcare systems now include psilocybin and MDMA [3, 4-Methylenedioxy- methamphetamine] treatment as options if they are provided in a medical facility. California bill 1012 is in review, which would establish a board of regulated psychedelic facilitators to license and systematize control of the use of psychedelic substances.

Personal Perspective

While this background provides context, we can learn a deeper truth by listening to someone who has been there. Sara is brave and generous enough to share her story.

“I’d never been part of a clinical study, so I was walking into an entirely new world,” says Sara. “Before this, I had spent a lot of time trying to find alternative ways to deal with my anxieties or depression. By the time I found the research group, my psychiatrist had deemed me treatment resistant.”

“The first study was using an esketamine nasal spray. Esketamine is the S enantiomer of ketamine. I knew of ketamine! I had tried IV ketamine, but I unfortunately wasn’t able to complete the six to eight treatment sessions, due to work taking me out of the city and it was an expensive endeavor that wasn’t covered by insurance. Esketamine was essentially ketamine, but it would be administered differently this time, and I wouldn’t have a therapist by my side. I was hopeful that it would help me and that my participation would help in getting this treatment more widespread.”

“The paperwork, blood draws, urine samples, and questionnaires, all made sense. When the study coordinator pulled out this mess of cords with nodes attached to them to place on my head, it made me feel like I was in some sort of sci-fi movie. I kept wondering if what was being measured looked ‘normal.’”

“For treatment, the doctor/therapist came in, asked a few questions, and pointed to a camera in the room so I could simply raise my hand, and they’d see it and come in. Then the nurse came in the room and handed me the nasal spray, which I’d administer myself. They walked me through it; one spray in each nostril, and wait 10 minutes to repeat the process. Then the nurse turned the lights off and left me to go on my little journey. I was terrified, being in a dark room alone, but I was open to the process, so why the hell not? I did raise my hand once or twice in that dark room. The doctor came in and grounded me until I returned to calm, and they’d leave me to journey. It’s hard to sum up my journeys, but here’s a bit from a journal entry after my first treatment:”

It feels like I’m going into a 2D world. Like I’m becoming the static you’d see on an old TV. Difficult to describe.

I started to cry. A heavy cry. Sobbing, you know, where you have trouble catching your breath.

The staff came in and helped me. We’d talked about setting an intention at the beginning. He asked me to remember what my intention was. Trust myself. My decisions. Just trust. “What does that look like?” he asked...

“The ocean,” I responded. Why the ocean? I don’t know. It’s vast. It’s deep. Has a lot of weight. It takes trust to dive in. It’s vast and unknown, like putting trust in someone else. Another person’s life is vastly different from my own. I don’t know their thoughts or how they think. And I love that. I love that difference. That variety.

But it’s also risky, incredibly risky to “dive in” with another person. What’s under the surface? I can handle it at first. It may even be adrenalin pumping, exciting. But then I become so exhausted. How much longer can I swim like this before I drown? Is it worth it?

How can I free myself to let myself go in the water? How can I take that dive and trust that it will be there and will provide safety? I just do. My trust is the most important. I spend most of my time worrying about pleasing others. But my approval or trust is vital. I know this deep down. I can do this.

“In the last session I had, I reached a black wall and fought going beyond it. I felt as if I’d die if I approached it. I surprised myself when I thought, ‘Well, if I die, I die!’ I can’t tell you how freeing that was. I then slid down this slide into an abyss that went beyond the black wall which I could have never fathomed. I think this was a big turning point for me. I finally let go and let myself release my iron grip on what I thought was living. Turns out, there’s a lot more out there. I still feel sad this was my last session. But life got in the way.”

“My second study was with LSD. Again, I did my best to clear any expectations that showed up, especially as there was a chance that I could receive all placebo pills. My family had a lot of hesitation. They had been informed their entire lives of the dangers of LSD and other psychedelics. They thought that people who did LSD wore colorful clothes, were free loving, didn’t respect our country, and many of them went mad! The going mad part seemed to be weighing the heaviest. I could see it in my parents’ eyes, the concern that they might lose me if I took part in this study. I felt some support, but it was more of a hesitant support.”

“During the study, I was poked about the amount I expected but questioned a lot more. I’d see someone on a video call to answer a series of questions about anxieties and depression. It wasn’t unusual for me to cry. Then, the coordinator would bring me to another room to answer another computer’s questions. Often, the questions were similar if not the exact questioning I had just gone through. This process was quite exhausting.”

“Dosing day was an adventure. I tried to put myself in the most comfortable place I could be, to clear my mind, to be open to whatever would come my way. The two Dosing Session Monitors (DSMs) met with me once prior to dosing day, which was good, but I still felt like they were strangers on dosing day. I wished one of the DSMs could be someone I’d been pouring my soul out to with those questionaries.”

“I could talk for days about the various experiences I had during dosing day. Some experiences I am still processing. A common theme throughout was that I saw externally what I was feeling internally. When I wasn’t sure of the DSMs, their faces turned scary, edges of the room were harsh and sharp. Unfriendly. In another moment, I felt safe and calm, the DSMs’ faces looked almost angelic, and the room was soft, glowing, and shimmery even. I was safe and comfortable to reflect on so many deep and meaningful things in my life. Honestly, time didn’t make any sense and I couldn’t tell you how things happened linearly. But I think initially unsettling, scared, then feeling in awe of some of the realizations of what my mind is capable of. Then bringing myself back time and time again to when I felt as calm as I have ever felt. In a field. Gently swaying grasses. A feeling of childlike wonder and contentment for my life.”

Conclusion

Traveling through the layers in which a clinical study with a psychedelic exists, from historical to public opinion, clinical data to one person’s experience is quite a journey. Everyone, including the sponsor, researcher, institutional review board (IRB), and participant, needs to be mindful of how the layers can impact each perspective. Doing this will maximize the potential benefits from the knowledge gained and minimize the risks of employing these powerful products.

References

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