What We Still Don't Know About Psychedelics in Cancer

"The more I've done this, it's now like 400 [psychedelic-assisted] treatments or so, and I feel like sometimes I know less now than when I started." This is tremendous humility coming from the leader of the world’s most active psychedelic research site. 

I recently sat down for a podcast conversation with Manish Agrawal, founder and CEO of Sunstone Therapies. Sunstone has conducted multiple clinical trials across several psychedelic compounds. Hundreds of treatment sessions. Years of firsthand observation.

If anyone should be positioned as "the expert" on psychedelic cancer care, it's Manish. So when he says "I'm the expert of nothing," I believe him. And I respect him for it. And I’m awed by his radical humility.

This kind of humility isn't weakness or uncertainty that should destabilize hope. It's deep curiosity and intellectual honesty in a field that's just begun to understand what it's investigating. During our conversation, we explored open questions that remain—not to suggest psychedelics don't work, but to identify where rigorous exploration still needs to happen.

Good questions matter as much as premature answers.

Question 1: Which Patients Benefit from Which Interventions?

Early research suggests psychedelics show promise for reducing psychological distress in cancer populations. But "cancer patients" represents an enormously heterogeneous group. And "psychedelics" encompasses multiple substances with different mechanisms and effects. And there are innumerable variables related to set and setting. 

The holy grail of modern oncology has been personalized medicine—matching specific patients with specific interventions based on their unique characteristics. We've gotten remarkably sophisticated at this for cancer treatment itself, using tumor staging, genetic profiling and biomarkers to determine which chemotherapies or targeted therapies will work best for which patients.

Could we apply similar thinking to psychedelic medicine?

"I'd love to have a study where I'm using all of those different compounds in different settings with different cancer patients and trying to understand which profile is better for which person," Manish told me.

This isn't just about patient phenotyping. It's about considering set, setting, and substance holistically. The right patient, in the right environment, with the right preparation, using the right compound at the right dose.

Early-stage cancer survivors might benefit from different approaches than people with end-stage disease. Someone with treatment-resistant depression might need different protocols than someone with adjustment disorder. Physical pain from surgery might respond differently than existential distress from terminal prognosis.

We don't know yet. These are testable hypotheses awaiting investigation.

"But it's a resource issue more than something where a priori we know why one is better than the other," Manish acknowledged.

The framework exists. The questions are clear. The resources to answer them comprehensively? Still being assembled.

Question 2: Is Less Actually More?

Conventional wisdom in clinical research generally assumes that larger doses produce higher efficacy and more side effects. But Manish is questioning that assumption based on observations in psychedelic research.

"I actually think less might be more," he said. "People having big doses have such a big experience, that they maybe take away 15% or 20% of what they could out of it. Whereas a lower dose, they may be more cognizant and able to get more out of it and use that integration over a longer period of time."

This hypothesis suggests lower doses might allow more agency during the experience. More connection to everyday reality. More ability to explore difficult psychological terrain in manageable increments rather than getting overwhelmed.

"It may not create the immediate effect the next day," Manish acknowledged. "But I think over time, they may be able to integrate more."

If validated through rigorous testing, this hypothesis could significantly change treatment protocols. But right now it remains an informed speculation based on clinical observation.

Question 3: Can Benefits Occur Without the Psychedelic Experience?

Some researchers are investigating whether psychedelics can be therapeutically effective without the intense subjective experience. Can neuroplasticity effects be separated from consciousness-altering effects? Do psychedelic medicines ‘work’ without the ‘trip’?

Manish raised related questions: "Is there a difference between the mind and the brain? How do you assess for that? What are subjective experiences? What is happening there?"

These questions sit at the intersection of neuroscience, philosophy, and clinical practice. Psychedelic researchers are exploring whether therapeutic benefits require the full psychedelic journey in the mind or whether the underlying physiological changes might occur independently in the brain. Do psychedelics work on the mind, the brain or both? 

The answer matters because it has implications for accessibility, safety screening, and therapeutic protocols. We don't have definitive answers. But we’re asking the right questions. 

Question 4: What About Physical Symptoms?

Most psychedelic cancer research has focused on psychological outcomes—depression, anxiety, existential distress. But what about the physical symptoms that accompanies cancer treatment? What about pain? What about neuropathy? 

"We did see that with some of our participants. I remember one gentleman particularly with prostate cancer. It’s not that his pain went away, but his relationship with the pain changed," Manish shared. "The pain didn't bother him as much. It wasn't that it went away, but it just wasn't affecting him."

Is that a psychological shift altering pain perception? Or is something happening physiologically? Historical psychedelic research in the 1960s actually began with pain management before pivoting to psychological symptoms. Will the modern psychedelic renaissance bring us full circle back to pain?

"I think some good pain studies would be very well warranted," Manish said.

Warranted indeed. But yet to be conducted among cancer patients. Another open question awaiting investigation.

Question 5: How Do We Provide Safe Access?

Looking ahead to potential FDA approval of psychedelic medicines, enormous implementation questions remain around both safety and access for people living with cancer. 

"Who is it safe for?" Manish asked. "What's the best setting? How do you prepare people for it? All the different aspects of a new specialty that is being born—how do you bring that into being?"

On the safety side: What are the key contraindications to ensure safe access? What about drug interactions with cancer medications? What about patients with cardiac conditions or other comorbidities? How do we ensure quality control and patient safety across multiple treatment sites?

On the access side: How do we train enough therapists to meet potential demand? How do we make this accessible through insurance coverage while maintaining appropriate safeguards? How do we address geographic barriers for patients who can't travel to major centers?

As Manish noted, prioritizing mental health in healthcare systems will be essential: "We tend to pay for procedures and medical devices, but not necessarily for mental well-being. I think prioritizing that as a society and acknowledging the impact that it has, and then really working with payers to be able to reimburse is going to help access."

These operational questions—balancing safety with accessibility—don't have easy answers. And that’s OK. Because we will find those answers as we move forward. Patient access and safety are critical objectives. So we may need to move slowly. And that’s OK too. 

What We Do Know

These open questions don't suggest psychedelics don't work or aren't worth exploring. The early research shows genuine promise. Manish's firsthand observations—watching people shift from stuck to moving, from despairing to connected—suggest real therapeutic potential.

But we're at the beginning of understanding these medicines in cancer contexts. The humility to acknowledge what we don't know is essential for conducting rigorous research that eventually provides answers.

As Manish put it: "We're just at the beginning of the beginning of understanding these drugs."

The beginning. Not the end. Nowhere close to comprehensive understanding.

And perhaps that's exactly where we should be—asking good questions, conducting careful research, remaining skeptical and curious in equal measure.

Because people living with cancer carry tremendous wisdom in our bodies. Our journeys have made us strong. We deserve research that matches our sophistication—research that doesn't overpromise, doesn't oversimplify, and doesn't pretend to know what remains genuinely unknown.

Good questions lead to good science. Good science leads to better care. Better care is what we're seeking.

Let's journey together, with both hope and humility.