Advancements in medicine and technology have allowed people with severe illnesses to prolong their lives. Although it provides additional opportunities to spend time with loved ones, it also extends the end of life. The period near death is often linked to psychological problems such as depression, worry, and a feeling of approaching death. The emotions typically stem from the limitations caused by their symptoms, like decreased independence and participation in activities that hold significance.

Initial studies have demonstrated the importance of psychedelics in alleviating anxiety and depression in end-of-life situations by prompting cognitive, emotional, and perceptual shifts over both short and long periods. Nevertheless, the incorporation of psychedelics in palliative and hospice environments is not commonly addressed.

This article explores the research studies that showcase the potential of psychedelics in aiding patients in managing depression and anxiety, as well as in enhancing their perspective on their circumstances. It also discusses the current situation of the legalization of psychedelics, potential side effects, and the future of their use.

Types of Psychedelics and How These Work

The National Institutes of Health (NIH) describes psychedelics as powerful psychoactive compounds that alter perception and mood. Indigenous communities view psychedelic substances as sacred and incorporate them into their spiritual and therapeutic rituals. Organic psychedelics are naturally created by fungi or plants, like ibogaine and psilocybin, whereas lysergic acid diethylamide (LSD) was synthetically developed in the 20th century by Western researchers.

The majority of the effects of psychedelics take place in the prefrontal cortex of the brain, which regulates emotions and perceptions of the world. There are three major categories of psychedelics as described below:

Entheogens bind with serotonin receptors in the brain. These receptors are also the target of various antidepressants). Since ‘entheogen’ is derived from the Greek word meaning god within, these psychedelics are believed to support spiritual development, instill feelings of sacredness, and provide new psychological insights. Examples include psilocybin, LSD, ayahuasca, peyote, and dimethyltryptamine (DMT).

Empathogens are believed to elevate ‘feel-good’ neurotransmitters in our system, such as dopamine, serotonin, and noradrenaline. This helps in developing emotional openness and feelings of empathy. Patients have reported experiencing loving feelings for others, a heightened sense of belonging, a stronger connection to the earth and everything in it, and an overall elevated mood. An example of this type of psychedelic is methyl​enedioxy​methamphetamine (MDMA) which is commonly known as ecstasy or molly.

Dissociatives block NMDA receptors associated with memory, creating feelings of detachment from one’s body yet keeping one aware of their surroundings. This helps patients distance themselves from the psychological and physical pain they are experiencing, hence reducing their ordeal to some extent. Ketamine is an example.

Science-Backed Evidence: Psychedelics for End-of-Life Anxiety 

While the specific ways in which psychedelics work as therapy are not fully understood, early indications show they enhance mental adaptability and aid in the formation of fresh outlooks on personal situations.

In 2016, a research study gave cancer patients with anxiety and depression a one-time dose of psilocybin (0.3 mg/kg) along with psychotherapy over seven weeks. Results showed instant, significant, and continual improvements in anxiety and depression. Moreover, patients reported a reduction in cancer-related disheartenment and an overall improvement in spiritual well-being and quality of life. Furthermore, a 6.5-month follow-up showed that psilocybin helped mitigate the anxiolytic and anti-depressant effects of cancer treatment and improved attitudes toward death.

Another study performed in 2022 compared psychedelics and non-drug experiences which changed an individual’s concepts about death. As opposed to the psychedelic group, the non-drug group was more inclined to report experiences of being unaware, medically deceased, and feeling that their life was at risk. However, both groups showed similar changes in attitude towards death after the experience, such as decreased fear of death, long-lasting positive effects, personal meaning, spiritual significance, and psychological insight. When comparing different psychedelic substances, individuals who took ayahuasca and DMT reported more intense and positive long-term effects of their experience compared to those who took psilocybin and LSD, which were very similar.

Patient Experiences: Taking Psychedelics for End-Of-Life Anxiety

For individuals who have positive reactions to psychedelic therapy, it is more than just a personal journey. Numerous patients describe improvements in their family relationships. Sometimes, this occurs when they begin having more candid discussions about the possibility or imminence of death.

There have also been different types of advancements in patient health due to psychedelic therapy, including deep understandings, transpersonal encounters, and sudden changes in emotions and self-perception that occur during psychedelic experiences. There is also a possibility that changes in the belief systems, self-perceptions, and mood states of these patients may be important factors that help improve conditions like depression. 

Certain research studies in end-of-life and palliative care utilized a specific questionnaire focused on measuring various aspects such as unity, reverence, transcendence of time/space, and ineffability in patients who were administered psilocybin. Nevertheless, for the majority, a crucial advantage of the treatment was the realization that they viewed themselves as distinct from their medical condition. This shows that psychedelic therapy alters the accounts an individual holds about their sickness and who they are, and assists them in discovering more about themselves and their existence, highlighting the uniqueness of this therapy.

However, the results of psychedelic therapy vary among individuals, and experts advise prospective patients to be open-minded and accepting and to leave their expectations and apprehensions at the door.

Are Psychedelics Safe for Treating End-of-Life Anxiety? Yes!

Although more large-scale and thorough research is required to make conclusive claims, the current evidence available from clinical trials suggests negligible adverse effects from the supervised use of psychedelics. This indicates that the side effects of using psychedelics and other dissociative substances outside of a clinical setting remain unknown.

Certain side effects reported by the patients involved in clinical trials include:

• fear and confusion

• anxiety

• nausea and vomiting

• headache

• fatigue

• high blood pressure

Using Psychedelics in Hospice & Palliative Care: A Walk-Through History & Legal Framework

Researchers have been experimenting with psychedelics since the 1950s when psychiatrists such as Humphry Osmond, who also came up with the term, first tried LSD-assisted psychotherapy. However, studies back then weren’t compliant with today’s rigorous standards, and hence their efficacy remains uncertain. 

Then, in the 1970s, studies using psychedelics virtually came to a halt in the United States after the Controlled Substances Act was passed. Later, in 2014, the popular American science magazine Scientific American demanded lifting the ban on clinical trials with psychedelics, paving the way to what came to be known as a psychedelic renaissance. 

Furthermore, right-to-try laws have helped gravely ill patients access psychedelics and other experimental drugs without waiting for FDA approval. These laws have also helped fuel significant psychedelic research. Currently, two psychedelic-based drugs are FDA-approved; ketamine as an anesthetic, and its derivative, esketamine for treating resistant depression. Moreover, the FDA granted breakthrough therapy designation to two preparations of psilocybin that were being evaluated for their efficacy and safety in treating depression and to MDMA for expediting research for its use in treating post-traumatic stress disorder.

In 2020, the state of Oregon was the first to authorize using psilocybin (psychedelic mushrooms) in combination with conventional therapeutic techniques. The state of Colorado came next, legalizing magic mushrooms on Election Day 2022. This decision will hopefully lead to further changes in Colorado laws to sanction the use of more plant-based psychedelics including DMT, ibogaine, and some types of mescaline, in June 2026.

Final Thoughts: Future of Psychedelics for End-of-Life Anxiety

There is preliminary evidence suggesting that psychedelic drugs can initiate mystical-type experiences in individuals dealing with end-of-life anxiety under controlled and supportive conditions. These experiences include improvement in negative outlooks, increased feelings of belonging, better mood, and a healthier perception of their situation.

However, challenges in selecting study participants, restricted legalization of dissociative drugs, and FDA regulations have restricted the information available on the subject. To validate the use of psychedelics in medical settings, especially palliative care, further research establishing the safety, effectiveness, and mechanisms of action of these drugs is critical.

Sources

Ross, S, Guss, J., Agin-Liebes, G., Malone, T., Cohen, et al. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology (Oxford, England), 30(12), 1165–1180. https://doi.org/10.1177/0269881116675512

Mary M., Sandeep N, Ethan S., Lisa N, Cody S, Roland G. (2022). Comparison of psychedelic and near-death or other non-ordinary experiences in changing attitudes about death and dying. PLOS One. 17(8): e0271926. https://doi.org/10.1371/journal.pone.0271926

Yu CL, Yang FC, Yang SN, Tseng PT, Stubbs B, Yeh TC, Hsu CW, Li DJ, Liang CS. Psilocybin for End-of-Life Anxiety Symptoms: A Systematic Review and Meta-Analysis. Psychiatry Investig. 2021 Oct;18(10):958-967. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542741/

Psychedelics gave terminal patients relief from their intense anxiety. Washington Post. https://www.washingtonpost.com/wellness/2024/01/13/psychedelics-terminal-illness-cancer/ 

Comparison of psychedelic and near-death or other non-ordinary experiences in changing attitudes about death and dying. PLOS One. Published: August 24, 2022. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271926 

Author: Saira Zulfiqar

Saira Zulfiqar is a pharmacist and medial writer with more than 15 years of experience in research and writing. She has written extensively on mental health, depression, grief, breathwork, meditation, psychedelics and well-being. Over the years, she has crafted impactful medical communications and generated insightful research publications, blogs, reviews, and research papers.