Can Psychedelic‑Assisted Treatment Redefine Emotional Care In Oncology?

By David Feifel, MD, Ph.D.

Oncologists increasingly recognize that mental health affects clinical outcomes in cancer therapy, prompting many cancer centers to employ psychiatrists as part of the care team. Treating cancer patients for anxiety and depression follows well-established guidelines, but for up to 19% of cancer patients (nearly one in five) who suffer from a psychological condition called adjustment disorder,^1-3 no FDA-approved treatment exists, and off-label treatment with depression medications has limited efficacy.

Research into a completely different therapeutic approach called psychedelic‑assisted treatment has already been shown to improve mental health in cancer patients and alleviate depression.^4-8 This approach may change the treatment paradigm for cancer patients, particularly the one in five with adjustment disorder who currently have no effective treatment. As a principal investigator in multiple studies of psychedelic‑assisted treatment for adjustment disorder, I have seen its potential to transform psychiatric care in oncology.

Why Target Adjustment Disorder?

A cancer diagnosis is traumatic, particularly for patients facing terminal disease. Aggressive or unsuccessful treatment can be traumatic in its own right. Unlike anxiety or depression, adjustment disorder is triggered by a traumatic cancer diagnosis or treatment. Rather than adjusting to the situation, patients quickly develop a disproportionate response, including persistent debilitating symptoms such as rumination, sadness, hopelessness, constant crying, anxiety, irritability, and even suicidal thoughts.^9,10 They become dysfunctional and unable to focus, sleep, bathe, or carry out normal daily activities.^9,10

For cancer patients, the normal activities that suffer may include compliance with cancer therapy, such as taking medications or attending in-office treatment visits. They may not maintain the social networks they need at this difficult time or effectively handle the financial side of their healthcare. Some are too despairing to make decisions about their own care. (“What’s the point?” is a question I often hear.)

Thus, without effective treatment, adjustment disorder can negatively affect cancer patients’ treatment outcomes.^1,11 With no treatment currently FDA approved for adjustment disorder, most patients are treated off-label with depression and anxiety medications. Few studies have examined their efficacy for adjustment disorder. SSRIs have been shown to be no better than placebo for adjustment disorder,¹² while short-term benzodiazepines are minimally effective for significant depressive symptoms.¹³

Searching for a different kind of solution, researchers have investigated psychedelic treatment for adjustment disorder, and preliminary studies have already shown promising results. A psilocybin analogue has been shown to improve spiritual well-being, quality of life, and feelings of hopelessness in patients with cancer.¹⁴ It has also been effective and well-tolerated for cancer patients with depression and anxiety.^4-8 Because I view psychedelics as a future game-changer in the field of mental illness, I have led several trials for various indications of psilocybin and other psychedelics. I was intrigued to consider whether this auspicious new tool in the pipeline could offer a unique approach to treating patients with adjustment disorder.

What Does Psychedelic-Assisted Treatment Look Like?

When patients with depression receive antidepressants and supportive therapy, we generally define positive outcomes in terms of diminished symptoms. Psychedelics have unique properties that we don't see with other types of treatments, and the outcomes of treatment are very different as well. I am now following those outcomes as a principal investigator on Reunion Neuroscience’s Phase 2 REKINDLE study, examining the use of a psychedelic psilocybin analogue, luvesilocin, for patients with adjustment disorder from a variety of serious illnesses, including cancer.

Luvesilocin treatment in the REKINDLE study follows a methodology similar to previous studies of psychedelics.  Participants are enrolled through outreach to current patients as well as referrals verified to meet the diagnostic criteria for adjustment disorder. The process of education and consent is key. Many patients have heard about psychedelic treatments in the media, and they are seeking out studies after hearing about positive results of earlier trials. A psychiatrist discusses the psychedelic approach in detail, explains what to expect, and schedules treatment.

The treatment environment for psychedelics plays an essential role in shaping the subject’s experience, in turn impacting the outcome of treatment. Thus, unlike other study protocols, protocols for psychedelics have specific standardized requirements for the treatment environment. Private treatment rooms with en suite bathrooms are visually calm and pleasant. Patients can wear eye shades and headphones with soothing music, sometimes chosen from a choice of playlists specified by the sponsor for additional standardization.

On the day of treatment, a trained facilitator meets with each patient and stays with them to monitor therapy. Patients feel safe because the facilitator is there in the room, and they know that medical support is nearby. This feeling of safety allows patients to get the most out of the experience.

Patients receive a subcutaneous injection of luvesilocin. As treatment takes effect, psychedelics have a very powerful capability to induce neuroplasticity in the brain, temporarily opening a window to allow it to create new pathways and connections. This state exists in children’s brains but becomes very limited after the mid-20s. Patients experience a different state of consciousness during treatment.

The experience lasts 3 to 4 hours, after which the patients return to their baseline state of consciousness. For safety purposes, patients stay in the clinic and are monitored for a total of 8 hours. Patients in this study are currently treated with just one session and are then assessed by the study team for the following six weeks to monitor changes in their adjustment disorder symptoms and possible side effects of the treatment.

With psychedelics, we see the effects of therapeutic treatment within 24 hours — very different from depression drugs that take weeks to show any change. The drug is also out of the patient’s system in 24 hours, so side effects are greatly reduced compared to antidepressants that must be taken on an ongoing basis. Rather than just experiencing a reduction in symptoms, my patients show fundamental changes in perspective. They tell me that the treatment experience allows them to reframe their trauma with greater insights into their situation. For example, patients with terminal health conditions like cancer have said that treatment allowed them to come to terms with their mortality. Recognizing that they are part of the larger universe where everything is connected, including life and death, they feel they will continue to exist after death as part of that larger universe. The transformation is very meaningful. Their quality of life improves, and they can be productive again at work and at home. They are better equipped to adhere to cancer therapy and work with their medical team to fight cancer.  

How Will This Change Cancer-Related Psychiatric Care?

The current landscape of psychedelic therapies represents a true innovation in psychiatric care, rather than a “me, too” incremental change. I see them potentially becoming the new standard of care for patients with cancer because they approach the psychiatric problems in a fundamentally different way. The speed of onset is typically within one day, rather than weeks. And in a revolutionary paradigm for psychiatry, the beneficial effects of psychedelics continue long after the drug has left the body. It is gone in 24 hours, but the psychological and biological benefits continue far beyond the life of the molecule. That's a very exciting change. The results we see across the literature are spectacular. Because of the short time they are in a patient’s system, psychedelics are not associated with the chronic side effects of conventional antidepressants that need to be taken every day.

Although sponsors do not have full autonomy over clinical trials, I hope that it may be possible to address some of the unique issues around compliance in blinded studies of psychedelics. Given the fast and distinct effects of psychedelics, patients who do not have a strong experience are often disappointed and suspect that they received an inactive dose. This makes it hard to motivate subjects of blinded trials to come back for follow-up visits, whereas patients are easier to retain if the initial blind randomization phase of the study is followed by an open-label phase.

Psychedelics have the potential not only to meet an unmet need for treatment of adjustment disorder but also to transform treatment for patients with depression and anxiety for whom traditional drugs and therapy are less than completely effective. Patients in cancer treatment can improve their peace of mind, their quality of life, and their ability to fight the disease. As we continue studies of this psilocybin analogue, we will learn more about the optimal interval for retreatment (for example, for patients with chronic depression) and its efficacy for different disorders, but the evidence for transforming cancer care is already mounting.

References:

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About The Author:

David Feifel, MD, Ph.D., is a neuropsychiatrist and neuroscientist. He is a professor emeritus of psychiatry at the University of California, San Diego, the founder and medical director of the Kadima Neuropsychiatry Institute in La Jolla, California, and a principal investigator of several studies, including the REKINDLE study.