Integrating Emotional Healing Through Psychedelics Into Everyday Oncology Practice

As interest in psychedelic-assisted therapy grows across oncology and palliative care settings, the use of psilocybin to address the emotional and existential distress experienced by patients with cancer is emerging as a powerful tool to help patients heal emotionally after healing physically. While most clinical trials involving psychedelics have been confined to academic centers or psychiatric settings, Manish Agrawal, MD, co-founder of Sunstone Therapies and former director of oncology at the Aquilino Cancer Center in Rockville, Maryland, has taken a different approach. His research places psilocybin-assisted therapy directly within the community cancer center—where most cancer care actually occurs.

In this interview with Pharmacy Times®, Agrawal discusses the rationale behind this site-of-care choice, early evidence suggesting durable reductions in anxiety and depression with just a single dose of psilocybin, and how this model may reshape emotional care for patients with cancer. Agrawal also explores the importance of psychological support, potential drug-drug interactions, and the pharmacist’s evolving role in psychedelic-integrated oncology.

Pharmacy Times: What led you to explore psilocybin in a community cancer setting specifically, as opposed to an academic or inpatient setting?

Manish Agrawal, MD: Well, it's a really good question, and it’s very intentional and deliberate, and it's because most of cancer care in the US in the world happens in community cancer centers and not in academic places. So, in order for people to get access to where they're getting their treatment, it had to be there. So that was a really important portion for me because most people with cancer get their cancer care in their community. It wasn't done in the inpatient because it was important to demonstrate that this can be done in a community cancer center and does not have to be done in a psychiatric inpatient hospital and in academic places, which is much more restrictive and difficult to access. The message to give to patients was where you get your care for your physical is also the place where you can get care for your emotional—and whole cancer care is all of that.

It also makes it much easier for people to access [this treatment]. So, patients on our studies, they were getting chemotherapy downstairs, but they could come upstairs and inquire about psilocybin, rather than going through a different entity, a different building, a different institution. It was much more continuity, and that's what you would want as a patient.

Pharmacy Times: From a pharmacologic standpoint, how do you interpret the sustained reduction in depression and anxiety following a single psilocybin dose, especially compared to traditional antidepressants?

Mycelium block of psilocybin mushrooms. Image Credit: © Deep Roots

Agrawal: Well, the mechanism of action is so different. The chronic selective serotonin reuptake inhibitors (SSRIs) use is meant to treat the symptoms and psilocybin—the intention is to have a deep effect on the brain, causing some degree of neuroplasticity where there can be potentially new perspectives on the cancer in their life. SSRIs are never intended to do that necessarily. So if you can get into a place of neuroplasticity and the amygdala and centers that are making a cancer patient feel fearful and unable to have reflection and really think about their cancer, then you're not going to really have that change. But if you are able to step into that and have a different perspective and reinterpret your life or the cancer in a way that's very meaningful and real to you, then that can have a long standing effect. Just like a cancer diagnosis is like a portal that someone enters, their life looks different then on, knowing, “Wow, I could be mortal,” similarly, a one-time deep experience the other way can also be a portal to look at their life differently, and SSRIs just don't do that.

Pharmacy Times: Were there any delayed adverse effects (AEs) or safety concerns reported over the 2-year follow-up period, and how were these monitored or managed?

Agrawal: So, the original study didn't follow people over the 2 years. When we followed up later, we did ask about [AEs], and there was no serious AEs from the patients from the study. So, nothing new necessarily emerged. If anything, I was surprised at how much people sort of grow and change with it. I do want to say it's a small study with a limited number of patients, so I don't want to see there's not long term toxicity, or that we don't need to monitor this much more closely, because I do think that in a larger population with more people, some of that stuff will emerge, but in our small study, we did not see that.

Pharmacy Times: How do the remission rates for depression and anxiety in this trial compare with those seen in pharmacologic standards of care, such as SSRIs or SNRIs, in patients with cancer?

Agrawal: Yeah, I mean, I think the comparison with SSRIs in this small study, it's almost 3x of what you would normally see in terms of efficacy, and that's why I'm excited about the new studies that we're doing now that are multi-center and a larger population, to see if those results hold up.

In oncology, certainly, and in most other diseases, what happens is in a small, single institution study, you see tremendous efficacy, but then as you get multi-center and larger populations, that [efficacy] usually diminishes somewhat, but doesn't always go away. But the change that was this much you don't typically see in SSRI studies at all. This is quite different from SSRIs—SSRIs are meant to be ongoing and longstanding, and when you taper somebody off of them, it's usually because it's not effective, but it still causes withdrawal syndromes. Whereas psilocybin is not intended to be chronic treatment. It's meant to be a 1- or 2-time treatment, and then it stops, maybe someone might need it again a year later. But it's never intended to be weekly, or every 3 weeks, or anything like that. So, it's quite a different paradigm of treatment.

Pharmacy Times: Did you observe any patterns in which types of patients (eg, by cancer type, stage, or demographic profile) were more likely to respond to psilocybin therapy?

Agrawal: There's been a lot in sort of end of life and advanced cancer, which I think is very important, and that's where most of the data is. But I was equally excited to see it worked in earlier stages, and so I don't think it's been talked about as much, but survivorship is as important a field in oncology as end of life, because people that live with cancer, many times they're suffering as much, and it's not always acknowledged or not always readily apparent—because they look and act like nothing is wrong and hair is growing back—but in truth, life has changed because of the cancer diagnosis. What we saw in our study is people that were cured of the cancer that were 3 years, 5 years, 7 years out, still found deep, meaningful benefit that allowed them to sort of reassimilate back into life.

Then it worked, really, regardless of the stage or type of cancer. It wasn't that one type of cancer was more effective. I think if any profile, I would say it's people that were genuinely wanting to change and to grow who were open to therapy or introspection benefited more than people who wanted this to be a magic bullet, and you take a psilocybin treatment and then it sorts of magically, sort of washes everything away. I think those benefited less, but the ones that were willing to lean in and do some work around what they learned, I would say, had a longer and more sustained benefit.

Pharmacy Times: How critical was the psychological support component to the observed outcomes, and do you foresee a standardized protocol being developed for this in clinical practice?

Agrawal: That psychological support is critical, and people are able to access these deep states when they're in relationship. I think the drugs by themselves have an efficacy, and that's a pharmacologic benefit, and I think there is that, but I think it's greatly enhanced, and safety is brought in with psychological support. So, I don't think it's an either/or. I think the drugs on their own have some benefit, and people have sensed that, but I think to have maximal benefit, and certainly to ensure safety, psychological support is vital to it.

I think there'll be some standardization. I think it'll be personalized. There are some basic principles that will be common to this type of treatment, and I think those will come out more of the principles behind it, and then it'll get individualized to that particular person. And so, paying attention to attachment styles, to their history, how you relate to them. And I think the crux of it is going to be a strong relationship. And then probably the technique on top of it is less important than the relational piece between the therapist and the patient.

I think this would be a long standing debate an issue, a lot of it's due just to economic and regulatory issues. We don't know how to think about therapy. It's expensive. People don't necessarily want to pay for it. I think if it was more accessible and reimbursable, it would just become standard. So, I think this is a big part of what's driving the wedge here.

Pharmacy Times: In practical terms, how might pharmacists collaborate with oncology or palliative care teams to facilitate safe integration of psychedelic-assisted therapy into treatment pathways?

Agrawal: Lots of patients have many medications as oncology patients, as well as supplements. I think more work needs to be done on drug interactions and blunting or perpetuating the effects of it. So I think having a pharmacist be part of the team, or certainly weigh in to help look at drug-drug interactions or considerations.

Then I think it'll be helpful, especially in the early days, to provide some reassurance for the oncologist, because it's kind of paradoxical, because oncologists feel comfortable with really quite toxic drugs that could kill people at the wrong dosages, and yet something that affects the mind but is relatively safe pharmacologically can be quite anxiety provoking for them, and to have a pharmacist involved could be helpful.

Pharmacy Times: Are there any known drug interactions pharmacists should be aware of when psilocybin is used alongside chemotherapy or supportive care medications?

Agrawal: It’s an area of ongoing research. I think the main thing is probably QTc prolongation. If they're on medications that prolong QTc, then you really want to make sure you have a good baseline electrocardiography and make sure it's not going to exacerbate that. We haven't seen that, but that's always a concern. I think that's a major one.

Pharmacy Times: Can you share any early insights from the ongoing, randomized double blind trial using 2 doses of psilocybin?

Agrawal: It's too early. Honestly, we haven't analyzed the data or looked at it. We're more than halfway done. I mean, anecdotally, there were certainly some people that 1 [dose] was sufficient. It seems like for some 2 helped. The 1 was helpful, but 2 take them took them further. But I don't want to say too much, because I just don't know, and I don't want to speculate that 2 doses is better than 1 until the study is complete.