Radiation therapy patients' interest in psychedelic-assisted treatment: survey results

Approximately 30–40% of cancer patients suffer from comorbid mood disorders such as anxiety and depression, with many developing such conditions after their cancer diagnosis [1, 2]. These mood symptoms not only are linked to lower treatment adherence and higher cancer mortality, but also incur a greater financial burden on the individual and health systems [3, 4]. Conventional management involves a combination of psychotherapy (e.g. cognitive-behavioral therapy) and medications (e.g. SSRIs), but these strategies are limited by delayed onset of action and lack robust evidence of effectiveness, particularly in the cancer population [5, 6]. Additionally, separately described cancer-related symptoms such as existential distress and demoralization—conditions which do not meet criteria for DSM-5 diagnoses and for which there are no specifically applicable medications—represent unmet needs that warrant novel therapeutic approaches to provide more comprehensive oncologic care and to combat the mental burden of a cancer diagnosis. [7]

An approach that has been recently tested for depression and anxiety symptoms in the cancer population is psychedelic-assisted psychotherapy (PAT). Research into clinical applications of psychedelic medications dates back to the 1960 s, and more recently emerging studies have demonstrated some benefits to LSD (lysergic acid diethylamide), psilocybin, ketamine, and MDMA (3,4-methylenedioxymethamphetamine) in treating treatment-resistant depression, suicidality, end-of-life anxiety, existential distress, PTSD (post-traumatic stress disorder), and substance use disorders [8–13]. For example, a double blinded, randomized placebo-controlled trial demonstrated that just two doses of ketamine administered 24 h apart achieved meaningful reduction in suicidal ideations in the short-term, while long-term follow up of patients who underwent single-dose psilocybin-assisted psychotherapy showed sustained reductions in depression, hopelessness, demoralization, and death anxiety in cancer patients up to 4.5 years later [8, 14]. A majority of the early clinical trials of PAT have centered around patients with terminal cancer. Within radiation oncology, 40–50% of treatments are given with palliative intent, and so there is significant overlap in the population who also have cancer-related mental health symptoms for which PAT may have a role. [15]

Despite growing evidence supporting the therapeutic use of psychedelic medications, they remain classified as Schedule I drugs, meaning they are considered to have no accepted medical use and a high potential for abuse. While it is thought that the legal classification, underground market, historical context, and anecdotes of negative experiences with psychedelics likely contribute to stigma and hesitancy around their clinical investigation and implementation, the opinions of cancer patients are understudied. To assess patient interest in PAT for treating cancer-related comorbid mental health symptoms, we performed a survey study of patients being treated with radiation therapy.

154 patients were screened for the survey, and 100 enrolled. Participants were informed that the study was voluntary and anonymous, and all provided consent and completed the full survey.

This study explored the interest in psychedelic-assisted psychotherapy among cancer patients undergoing radiation therapy, revealing that nearly half of the respondents were open to such treatment for managing cancer-related mental health conditions. Notably, interest in PAT was higher among those with greater depressive symptoms, poorer spiritual well-being, higher demoralization, worse quality of life, and more pain—symptoms that are targeted with PAT.

Understanding the current status and potential applications of psychedelic medications in the United States requires examination of the historical context. In the mid-twentieth century, psychedelics were initially investigated for their therapeutic benefits in psychiatry, with particular interest in their ability to address mental health conditions such as depression, anxiety, PTSD, and addiction [21–23]. During this period, these substances were frequently administered in clinical settings to evaluate their effects on mood, cognition, and behavior. However, as the 1960 s progressed, recreational use of psychedelics surged, particularly within countercultural movements, and substances like LSD, psilocybin, and mescaline became emblematic of the broader anti-establishment sentiments [24]. As their popularity grew, so did public concerns about the potential risks of these substances, including their safety profiles and their capacity for abuse. In response to these concerns, the Controlled Substances Act of 1970 was enacted, which categorized substances into five schedules based on their potential for abuse, recognized medical use, and relative safety. Psychedelic substances became classified as Schedule I drugs. Some argue that this classification was influenced more by the political and social climate of the time marked by a growing"War on Drugs"narrative and fear of the counterculture rather than by definitive scientific evidence. At the time, ongoing research had already suggested potential therapeutic uses for psychedelics, but these findings were overshadowed by the political context. [25]

Following their Schedule I classification, psychedelic research virtually ceased for several decades. However, at the turn of the century, a resurgence of interest in the therapeutic potential of psychedelics emerged. Recent clinical trials have demonstrated promising results for the use of psychedelics in treating mental health symptoms, including several small randomized controlled trials demonstrating that even a single high-dose psilocybin session significantly reduced depression and anxiety by in patients with life-threatening cancer in about 80% of patients at 6-month follow up [8, 10, 11]. Both the scientific community and public interest have recognized this movement, as demonstrated by the FDA’s issuance of a draft guidance for psychedelic clinical investigations in June 2023. [26]

There are limited data into the patient perspective of psychedelic medications. In a survey of athletes, 61.2% expressed willingness to engage in PAT for persisting post-concussion symptoms, and among cancer patients in New Zealand, 59% were open to considering PAT for psychological distress [27, 28]. The results of our study support that sentiments towards therapeutic use of psychedelic medications may be shifting, with nearly half of patients treated with radiation therapy expressing some interest in psychedelic therapy to combat cancer-related mental health conditions. Notably, the main reason for hesitancy towards psychedelics is the lack of information. Furthermore, those who reported higher levels of depression, worse spiritual well-being, worse demoralization, worse quality of life, and more pain, symptoms that are targeted for psychedelic-assisted therapy, were more likely to be receptive to it. Interestingly, individuals with higher levels of anxiety demonstrated a reduced interest in psychedelics. Potential explanations include that patients with generalized anxiety disorder may perceive PAT as less targeted for their condition, given the current focus of clinical trials on depression, PTSD, and existential distress. Additionally, heightened anxiety may predispose apprehension towards novel treatments.

Limitations of this study include the innate selection and framing biases of a voluntary survey study, small sample size, and heterogenous diagnoses and prognoses. Future directions will incorporate the perspectives of physicians and other providers toward PAT, sub-analysis by cancer type or prognosis, and impact on HRQoL or survival with administration of palliative psychedelic therapy. To aid in integrating psilocybin-assisted psychotherapy into healthcare systems, Dorval et al. propose specific recommendations of actionable steps emphasizing the need for regulatory reform, clinician education, dedicated treatment infrastructure, and public awareness initiatives to ensure equitable access in palliative care settings. [29]

This study highlights a substantial interest in PAT among cancer patients undergoing radiation therapy, particularly among those facing significant mental and physical health burdens, including depression, demoralization, pain, and poor quality of life. The primary barrier to potential interest appears to be a lack of information, underscoring the need for education and outreach to address misconceptions and inform patients about the completed and ongoing studies of PAT. Our findings suggest that there are unmet symptom needs in the oncology population and that there is significant patient interest in the clinical applications of PAT. Further research in the safety, efficacy, and implementation of psychedelics for the oncology population would be welcomed by patients.

Additional file 1.