Integrating Psilocybin-Assisted Psychotherapy in Comprehensive Cancer Care

Micheal P. Bogenschutz, MD, discussed addressing unmet needs, implementation, and adverse effects related to psilocybin-assisted psychotherapy in cancer.

Michael P. Bogenschutz, MD, director of the NYU Langone Center for Psychedelic Medicine and professor of Psychiatry at NYU Grossman School of Medicine, discussed insights related to the efficacy, implementation, and safety profile of psilocybin-assisted psychotherapy (PAP) in patients recently diagnosed with cancer.

Bogenschutz spoke with CancerNetwork® regarding the publication of a pooled analysis study of 2 phase 2 trials assessing psilocybin preceded by and followed by psychotherapy for patients with recently diagnosed cancers.^1,2 The pooled analysis sought to assess a broader array of outcomes than the original studies, with improvements observed in anxiety(P = .0049), depression (P = .0007), interpersonal sensitivity (P = .0005), obsession-compulsion (P = .0002), hostility (P = .009), and somatization (P <.0001).³

He initially touched upon the significance of the results from the pooled analysis, which Bogenschutz emphasized attempted to assess a broader array of psychiatric symptoms than the original 2 studies. He further discussed the potential for PAP to address an unmet need in patients recently diagnosed with cancer who may be facing psychological challenges.

Bogenschutz outlined PAP integration strategies, including in-house comprehensive cancer care integration or a referral system. He covered adverse effects (AEs) associated with psilocybin, particularly acute mind-altering and sympathomimetic effects. Furthermore, Bogenschutz discussed the importance of psychotherapy in tandem with psilocybin use, before highlighting the lasting impact of psilocybin dosing on patients with cancer-related psychological challenges.

PAP was assessed by a pooled analysis of 2 phase 2 crossover trials. What is the significance of the results?

Bogenschutz: This publication was a follow-up to the 2 primary publications, which came out in 2016. Those were 2 independent but fairly similar, small, randomized controlled trials testing the efficacy of psilocybin for depression and anxiety symptoms related to a life-threatening and potentially fatal cancer diagnosis. Those 2 studies combined independently, were small, so there was value in combining the trials and looking at the pooled outcomes, but also focusing on a broader array of outcomes than were primarily assessed in them. The papers focused on depression and anxiety symptoms, and this paper, looking at the 2 studies together, also focused on a broader array of psychiatric symptoms that people may have been experiencing.

What unmet need would this treatment help to reduce?

Bogenschutz: There are not any effective medications to help [patients with] psychological challenges presented by a serious cancer diagnosis. If [patients] have major depression, they can be treated with antidepressants. They can be treated with medicines for anxiety. The antidepressants do not appear to be particularly helpful in this population, and they do not address what the underlying cause is, which, in many cases, is [having] this existential crisis of one’s own possible or probable death in the near future.

In some ways, I tend to think about this situation as an adjustment reaction. [Patients have] a challenging situation, and they may become symptomatic or become incapacitated because of the psychological challenges. The psilocybin-assisted treatment, in some ways, acts like any other medication––to treat the symptoms. There are studies for major depression independent of a cancer diagnosis demonstrating enduring effects on depressive symptoms for weeks to months after a single dose of psilocybin.

In this population, one of the ideas behind how this works is that the experiences that [patients] have under the influence of psilocybin may help them better come to terms with the reality of death and what that means and to find some acceptance and meaning in the face of a challenging situation.

How might you see PAP use implemented into clinical practice for patients with cancer?

Bogenschutz: We are still in the early stages of demonstrating safety and efficacy [for PAP in patients with cancer]. Of course, patients with cancer are already engaged in medical treatment, and they have a team that they are working with to treat their cancer. In that context, it is normal for patients to be referred for psychiatric evaluation if they are having symptoms related to the cancer diagnosis or otherwise. This is something that would need to be incorporated into the behavioral health aspects of comprehensive cancer treatment.

That could be done either by building the capacity within the cancer center for providing psilocybin-assisted treatment or by developing referral networks whereby the cancer center could refer to a local provider who is skilled, has whatever credentials are ultimately required to use psilocybin clinically, and has enough experience with [patients with] cancer that they are able to provide that that service on a referral basis.

On one hand, we are certainly not at the point of implementation, but on the other hand, it is important to be thinking about the challenges and unique aspects of this treatment that will need to be dealt with to make it widely available to patients [with cancer] who may benefit [from its use].

Are there any toxicities or AEs associated with psilocybin, other than anxiety, that stand out to you?

Bogenschutz: There are risks and potential AEs [with psilocybin]––the main ones have to do with the acute mind-altering effects of the drug. During a session, [a patient’s] state of consciousness is altered quite dramatically. Some patients––it is not predictable who it might be––can become quite overwhelmed or fearful. [They may] fear that they are losing their mind or that they are, in fact, dying, or have other kinds of transient paranoid thoughts or delusional or strange ideas.

Those [mind-altering effects] almost always resolve within the acute period. Once the drug effects wear off, after 6 hours or so, most people are back to a perfectly normal state of consciousness. There are occasionally residual symptoms that can take longer to resolve, but that is uncommon. It is quite common for patients to have strong and sometimes distressing emotional states during the acute phase of the treatment. That is why it is important to have skilled clinicians with the patient for the entirety of the drug administration session, which is usually 8 hours or so. Beyond that, the medical risks of psilocybin are quite low in [patients who are] carefully screened.

There is not a lot of toxicity. The main potential issues are moderate sympathomimetic effects [with] psilocybin. Blood pressure may go up by 20 points for systolic and 15 for diastolic, on average––it varies. Heart rate will go up a bit, usually not above 100 [beats per minute], but that puts some strain on the heart. People with coronary artery disease or high risk of stroke, generally, have been excluded from the trials with psilocybin. Other than that, physiologically speaking, it is a safe drug as far as we know.

Is there anything else related to PAP or the pooled analysis study that you would like to highlight?

Bogenschutz: One of the interesting things about psilocybin is that there may be some disorder-specific effects––such as what we talked about in cancer––there may be a particular value. It is helping patients to work on a psychological level with the challenges of reacting to a cancer diagnosis. There seem to be effects on major depression, also that may be more biological by basis.

The best understanding currently is that psilocybin enhances the potential for neuroplasticity in some specific ways and in some non-specific ways. There is a general antidepressant, anti-anxiety, and short-term anti-addictive effects in terms of improving mood, improving sense of well-being, and decreasing the craving to be in some other state. It also appears to, in a more non-specific way, enhance the ability of patients to learn new things, think in different ways, and see themselves in the world in different ways. That is where psychotherapy comes in, because there may be some effects of the drug that happen automatically because of what the drug does to the brain, and there may be other effects of the drug that require ongoing work by the patient, in collaboration with a therapist, or some program to help them make the behavioral changes, the cognitive changes that [...] they want to make in their life overall.

It is interesting in that way for those of us who are studying this, because of the interactions between the basic pharmacology, the intention of the patient, and the therapeutic environment in which this treatment is occurring. The other thing to stress about psilocybin in general, and psychedelic treatments even more broadly, is that the effects of a single dose of the drug, in many cases, will persist for weeks and months after the administration. This is different from any other medications that we are using in psychiatry. There appear to be long-term changes that can occur as a result of these relatively brief treatments.

There are also a lot of implementation challenges that have to do with the need to have the patient sitting under close supervision by trained professionals for a whole day to receive a single treatment. There are many unanswered questions about how many treatments are needed, what the ideal environment is, what the psychotherapeutic platform is, what aspects of psychotherapy are necessary, and which ones are not so necessary. [Also,] how can this be done in a way that is scalable, as affordable as possible, and available to all patients––not just patients who have enough money to pay the considerable cost that will likely be attached to these treatments? Those are all things about psilocybin in general.

The one other thing I wanted to mention about the particular paper that we are talking about is that the value of this paper was to look at this broad spectrum of psychopathology, including not just depression and anxiety, but aspects that are associated with both mood and anxiety, [as well as] psychotic disorders. One of the reassuring findings was that there was no increase in psychotic and psychosis or paranoia associated with the administration of psilocybin. In this study, the patients who were psychotic to begin with would have been screened out of the study. [However,] there was no increase, and numerically speaking, a decrease in paranoia and psychosis symptoms patients were having after they received psilocybin.

There were also significant improvements in the other domains that were assessed, which included interpersonal sensitivity, obsessive-compulsive symptoms, hostility, and somatization. Some of [these domains] are related to anxiety, adjustment disorder, or depression, but it speaks to the broad spectrum of activity that psilocybin seems to have as well as the wide range of behavioral health benefits that patients can experience when they receive this treatment under the proper conditions.

References

1. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 2016;30(12):1165-1180. doi:10.1177/0269881116675512
2. Griffiths RR, Johnson MW, Klinedinst MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
3. Petridis PD, Grinband J, Agin-Liebes G, et al. Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nat Mental Health. 2024;2:1408-1414. doi:10.1038/s44220-024-00331-0