Psychedelics for End of Life Anxiety
Overview: This blog delves into the topic of end-of-life anxiety in patients with terminal illness and explores the potential of psilocybin-assisted therapy as a promising approach for mitigating existential distress. Drawing on research studies, it discusses the challenges of addressing anxiety in terminally ill patients and highlights the positive outcomes observed with psilocybin, LSD, MDMA, and ketamine. The unique characteristics of psychedelic-assisted therapies compared to conventional medications are emphasized, shedding light on the potential of this novel approach for improving end-of-life care. However, further research is needed to better understand the limitations and long-term effects of psychedelic-assisted therapy in this population.
What is End-of-life Anxiety?
End-of-life anxiety is a frequent concern for individuals who are nearing the end of their lives due to terminal illness. These patients must grapple with the existential challenge of confronting the uncertainty of what comes after death, or the potential loss of their sense of self. This can be a daunting and often terrifying experience, as they face the unknown landscape ahead.
For some, end-of-life anxiety may be experienced as rather mild, characterized by a lingering sense of restlessness and irritability. While, for others, end-of-life anxiety can be more severe, manifesting in disconnection, an inability to focus, crippling insomnia, and a heavy feeling of impending doom.
For example, it is common for cancer patients to develop seriously debilitating psychiatric distress, with rates of anxiety and depressive disorders as high as 40% in hospital settings.
Clinically significant anxiety and depression among cancer patients are associated with a variety of negative outcomes, including decreased quality of life, decreased cancer survival rates, decreased treatment adherence, prolonged hospitalization, and increased suicidality. The mental distress experienced by those facing their departure from known life is also associated with demoralization, hopelessness, isolation, and a lack of meaning.
Factors Affecting End-of-life Anxiety
Unfortunately, medical providers may sometimes be unaware of the mental toll of imminent death, or may be deceived by the outwardly composed facade of patients who take pride in maintaining a brave front. As a result, symptoms of existential distress may go unnoticed or inadequately addressed.
The fear of dying can manifest in covert ways and may be expressed through symptoms that may not immediately seem related to one's mortality. This can make it challenging to identify and address the underlying existential distress experienced by terminally ill patients.
Several factors can exacerbate or add to the complexity of one’s anxious state. Not talking about what is happening out of fear of negatively affecting loved ones, for example, although entirely understandable, may have the unintended consequence of compounding feelings of agitation, irritability, and helplessness.
Lingering debt, dispiriting regrets, and religious quandaries, too, can taint one’s final months or years with unwanted confusion and stress, not to mention the crippling pain that so often accompanies life-threatening illnesses like cancer.
Experts agree that it is normal for individuals to experience anxiety when confronted with the novelty and uncertainty of death. However, it is crucial to differentiate between common end-of-life anxiety and pathological end-of-life anxiety, which can be profoundly debilitating.
Regardless of its severity, prompt treatment is essential for end-of-life anxiety, and psychedelic-assisted therapy shows promise as a potential therapeutic approach.
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Psychedelics for End-of-Life Anxiety: The Research
Given the high level of attention that psychedelic substances attract, it can be easy to think of psychedelic-assisted therapies as mere drug treatments. However, there are significant differences between psychedelic-assisted therapies and the daily dosing of conventional medications.
Conventional medications for mental health conditions, such as selective serotonin reuptake inhibitors (SSRIs), are usually administered one or more times daily and are thought to produce therapeutic effects by producing sustained changes in brain connectivity. However, these medications may take several weeks or months to exert their effects, and may come with unpleasant side effects.
Unlike SSRIs, psychedelics are typically administered just once or in a series of 2-3 times in a living room-like environment and in conjunction with non-directive, supportive psychotherapy delivered before, during, and after sessions. Also, psychedelics alter brain connectivity for short periods, yet preliminary evidence suggests that psychedelic-assisted therapies can produce rapid, robust, and sustained improvements in psychological well-being.
Up until recently, clinicians have had very limited tools at their disposal to help alleviate end-of-life anxiety. Research suggests that psychedelic-assisted therapy could constitute a new frontier for end-of-life care. However, researchers acknowledge that the mechanism by which psychedelic-assisted therapy reduces death anxiety has not been fully established.
Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer
In January of 2011, Jama Psychiatry published a study entitled ‘Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer’. Psilocybin is the active ingredient in magic mushrooms.
Led by Dr. Charles Grob, UCLA professor and co-founder of the Heffter Research Institute, researchers administered 2 relatively small doses of psilocybin (0.2mg/kg) spaced several weeks apart to twelve advanced-stage cancer patients. All patients had received a DSM-IV diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder, or adjustment disorder with anxiety.
During psilocybin sessions, patients reported a range of psychedelic effects, such as positive derealization, positive depersonalization, altered sense of time, positive mood, and synesthesia. Patients were supported by the treatment team and experienced significant reductions in depression and sustained decreases in anxiety, which lasted for at least 6 months.
Psilocybin's Long-lasting Impact on Depression and Anxiety in Cancer Patients: A Randomized Double-blind Trial
Subsequently, researchers from Johns Hopkins Center for Consciousness and Psychedelic Research, led by Dr. Roland Griffiths, a professor of psychiatry and neuroscience, conducted a randomized double-blind trial with 50 patients who had a life-threatening cancer diagnosis and comorbid anxiety and/or mood symptoms. The study compared two doses of psilocybin, one high (22 or 30 mg/70 kg) and one low (1 or 3 mg/70 kg), which were administered to patients in capsules that looked identical
Building on Grob et al.'s previous findings on psilocybin's potential as an anxiolytic, the study revealed that a single high-dose psilocybin session led to significant reductions in anxiety, as reported by clinicians and self-assessed by participants. 76% of the participants experienced substantial decreases in anxiety, and these improvements persisted over time, with 83% of participants still showing clinically significant reductions in anxiety even 6 months later.
In addition to producing significant decreases in anxiety, psilocybin-assisted therapy was observed to:
- Decrease symptoms of depression
- Decrease symptoms of mood disturbance
- Increase quality of life
- Increase life meaning
- Increase death acceptance
- Increase optimism
Psilocybin for Cancer-related Anxiety: Promising Findings at NYU
In a study conducted at New York University around the same time, researchers conducted a double-blind, placebo-controlled, crossover trial with 29 patients suffering from cancer-related anxiety. The results showed that a single dose of psilocybin (0.3 mg/kg) produced significant reductions in end-of-life anxiety in 60-80% of participants. The treatment led to decreased demoralization, hopelessness, and existential distress, while also improving spiritual well-being, quality of life, and attitudes toward death
The authors reported that 57% of participants in the study continued to show clinically significant reductions in anxiety even 3.5 to 5.5 years after their psilocybin treatment. Additionally, 71-100% of participants rated their psilocybin experience as one of the most personally meaningful and spiritually significant experiences of their lives.
Efficacy of LSD-Assisted Psychotherapy for End-of-Life Anxiety
In 2014, Swiss physician for psychiatry and psychotherapy Dr. Peter Gasser facilitated two LSD-assisted psychotherapy sessions 2 to 3 weeks apart in 12 patients with anxiety associated with life-threatening diseases as part of phase 2 double-blind, active placebo-controlled, randomized clinical trial.
Patients received 200 micrograms of LSD in a safe and pleasant room in a private practice office, where they were supported by a male/female co-therapist team, embedded within an ongoing psychotherapeutic process including preparatory and integrative sessions.
Congruent with some studies from the 70s, LSD produced a significant reduction in end-of-life anxiety as experienced daily. The more stable tendency to attend to, experience, and report anxiety (trait anxiety) showed a trend toward reduction, an effect not typically observed in short-term psychotherapy. These reductions in anxiety were stable over time as demonstrated by the 12-month follow-up.
Interestingly, results demonstrated the most robust decreases in anxiety after the second LSD session, suggesting that at least two LSD-assisted psychotherapy sessions may be necessary to optimize therapeutic effects.
MDMA for End-of-Life Anxiety
MDMA-assisted psychotherapy has shown efficacy in the treatment of post-traumatic stress disorder (PTSD) in clinical trials conducted by Multidisciplinary Association for Psychedelic Studies (MAPS). A pilot study published in 2020 suggests that MDMA-assisted psychotherapy could also be an effective treatment for moderate to severe end-of-life anxiety and other psychological distress related to life-threatening illnesses.
In this study, the primary analysis indicated that participants who received 125 mg of MDMA (with an optional supplemental dose of 62.5 mg administered 90-150 minutes after the initial dose) as a therapeutic adjunct experienced greater reductions in anxiety compared to the placebo group (which received 125 mg of lactose). However, it's important to note that these differences between groups did not reach statistical significance.
MDMA-assisted psychotherapy was also observed to improve sleep, global functioning, psychological and physical well-being, self-compassion, mindfulness, and attitudes regarding death.
The findings of this study provide preliminary evidence to suggest that MDMA may be an effective therapeutic aid for those suffering from end-of-life anxiety associated with life-threatening illnesses, and can inform development of larger clinical trials to further examine this novel treatment approach.
Palliative Care and Anxiety: Promising Results with Ketamine - A Pilot Study
A 2020 pilot study investigated the anxiolytic effects of the fast-acting antidepressant ketamine in 8 palliative care patients. Results showed that a single administration of ketamine produced a significant reduction in anxiety compared to the control group. Despite some limitations to the design, this study may be the first step toward approval of ketamine for end-of-life anxiety.
The findings suggest that a single administration of ketamine may improve psychological distress in patients receiving palliative care, potentially producing a significant reduction in anxiety symptoms.
Notably, ketamine has also demonstrated clinical efficacy for social anxiety disorder, treatment-resistant depression in patients receiving hospice care, and intractable cancer pain, suggesting that it could potentially be a useful multi-functional palliative care treatment.
Challenges and Limitations of the Studies
It's worth mentioning that despite the promising findings, the studies discussed in this blog have some limitations that should be taken into consideration.
These limitations include potential placebo effects and variability in post-treatment contact, which could impact the interpretation of results. Additionally, some studies lacked double-blind assessment for high-dose efficacy and independent validation for measures of positive changes and symptom reductions. Blinded clinician ratings and small, predominantly white, highly educated samples also limit generalizability in some cases.
Furthermore, some trials had limitations such as small sample size, non-nationally representative patient populations, crossover designs that may have impacted the interpretation of clinical benefits, and controls with limited blinding.
These limitations highlight the need for further research and cautious interpretation of the results in the context of these limitations.
Explore By Substance
5-MeO-DMT
5-MeO-DMT (5-methoxy-N, N-dimethyltryptamine) is a short acting, serotonergic psychedelic, found naturally in the venom of the Sonoran Desert Toad (Bufo Alvarius). 5-MeO-DMT is gaining popularity as an effective tool for spiritual exploration and healing due to its extremely powerful psychoactive effects.
Ayahuasca
What is unique about ayahuasca is that it is a concoction of two plants, the combination of which is essential for the ayahuasca experience. Combining two plants to use as medicine may not seem groundbreaking in and of itself, but the fact that if one is taken without the other, the experience is entirely different, and arguably non-existent, is what makes the discovery of ayahuasca so surprising.
DMT
For millennia indigenous-American tribes have consumed N,N-dimethyltryptamine (DMT) as a key ingredient in sacred botanical brews, such as ayahuasca, and snuffs, such as yopo, as part of religious ceremonies in Central and South America.
Ibogaine
Ibogaine is a naturally occurring indole alkaloid derived from the roots of an threatened species of perennial rainforest shrub called Tabernanthe iboga. Ibogaine, which is believed to have potent anti-addictive properties, has been used by the indigenous peoples of central west Africa for centuries.
Ketamine
Though ketamine gained a reputation for being dangerous and easily misused and abused, it wasn’t until 1999 that the US classified it as a Schedule III controlled substance. While it is often associated with the party scene, ketamine therapy is helping change the lives of many with severe depression, PTSD, OCD and even chronic migraines.
LSD
In 1938, a Swiss chemist by the name of Albert Hofmann, working out of Sandoz Pharmaceuticals, became the first man to synthesize Lysergic Acid Diethylamide (LSD). Active at the microgram level (one-thousandth of a gram), LSD is the most potent psychoactive drug known to humankind.
MDMA
The MDMA molecule bears structural resemblance to stimulants and some psychedelics, invoking feelings of euphoria, empathy, and boundless energy. MDMA also intensifies sensory perception, enhancing one’s appreciation of music and color which makes it one of the most popular drugs among festival-goers and electronic dance music fans alike.
Mescaline
In the 16th century, Spanish chroniclers attempted to eradicate ritual use of peyote cactus among indigenous American cultures, which led to the plant’s eventual prohibition in 1720. In the face of adversity, several indigenous communities righteously persevered, continuing and preserving their sacred practice in clandestine secrecy, and even managing to spread it widely over the last 150 years.
Peyote
Peyote is a green spineless cactus that contains the classic psychedelic compound mescaline. Numerous Mesoamerican cultures, including the Huichol (Wixárika), the Cora (náayeri), the Tepehuanes, the Tonkawa, the Mescalero, and the Tarahumara (Rarámuri) have long regarded the plant as sacred, using it in spiritual and healing ceremonies for millennia.
Psilocybin
While evidence suggests that psilocybin mushrooms have been historically used in ritual settings for spiritual and medicinal purposes, they have gained popularity for recreational use, and clinical research on the therapeutic effects of psilocybin is promising.
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Salvia divinorum
Salvia is a psychotropic flowering herb from the Lamiaceae, or mint, family. Salvia’s large green leaves contain the powerful psychoactive compound, salvinorin A. Salvia leaves are used for medicinal and religious purposes by Mazatec shamans in the Mexican state of Oaxaca, and they are often used recreationally in the west.
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San Pedro
Since prehistory, San Pedro has been instrumental to Peruvian cultural traditions. in northern Peru in particular, it has been a tool to facilitate the shaman’s ‘‘journey’’ for healing purposes. Throughout this period, the visionary cactus has been known by many names, including huachuma or achuma.
