How Psychedelic Drugs Can Aid Patients at the End of Life

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Dr Roland Griffiths.

In 2016, Griffiths and his team at Johns Hopkins University in Baltimore published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with the New York Times in April 2023, he stated that after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people, ‘Come on, wake up!'”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the US Food and Drug Administration (FDA).

In 2022, Maia and a colleague from ICARO, Dr Ana Cláudia Mesquita Garcia, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, nine (45%) used LSD, five (25%) psilocybin, two (10%) dipropyltryptamine (DPT), one (5%) used ketamine, and one (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post-administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Dr Stephen Ross, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double-blind, and placebo-controlled and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off-label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Dr Alessandro Campolina, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Dr Toshio Chiba, chief physician of the Palliative Care Service at Icesp, emphasizes that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,'” said Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Dr Marcelo Falchi, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine,” he said.

In his last months of life, Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.