In their present resurgence as a potential therapeutic adjunct, psychedelic drugs like lysergic acid diethylamide (LSD), psilocybin (the active ingredient in magic mushrooms), and MDMA (also called ecstasy or molly), have demonstrated powerful healing properties across a variety of health conditions.
To highlight but a few, researchers have shown that psychedelics, together with psychotherapy, can be powerfully effective aids in the treatment of depression, post-traumatic stress disorder (PTSD), and substance-use disorders.
But, perhaps one of the more interesting examples of psychedelics’ therapeutic tendencies, is their profound ability to alleviate the suffering of those devastatingly compromised in their final years by end-of-life anxiety associated with life-threatening illnesses.
In the 1950s and 1960s, trailblazing psychedelic researchers conducted trials with hundreds of cancer patients and found that psychedelics, in particular LSD, could significantly alleviate anxiety, depression, and pain, while improving sleep and quality of life.
With antidepressants and psychosocial interventions demonstrating merely limited and inconsistent efficacy in treating existential and spiritual distress, there is a compelling need for contemporary researchers to build upon the seminal work of their predecessors and develop novel treatments that can safely improve the psychospiritual states of people diagnosed with life-threatening illnesses.
Up until recently, clinicians have had very limited tools at their disposal to help alleviate end-of-life anxiety. Psychedelic-assisted psychotherapy could constitute a new frontier for end-of-life care, and perhaps even produce a mystical experience that goes beyond the reduction of suffering.
End-of-life anxiety is a common complaint among terminally ill patients, who, confronting the existential challenge of dealing with the uncertainty of life after death, or lack thereof, and the potential end to their sense of self, are faced with the oft-terrifying landscape of the great unknown.
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 considerably 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.
Unfortunately, perhaps unaware of the mental toll of imminent death, or having been tricked by the psychologically sound persona of proud patients, medical providers often fail to pick up on and/or insufficiently address symptoms of existential distress. In his latest book, esteemed existential psychotherapist Irvin Yalom explains, “though fear of dying can immobilize some people, often the fear is covert and expressed in symptoms that appear to have nothing to do with one’s mortality.”
Of course, there is an array of confounding factors that 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 one’s feelings of agitation, irritability, and helplessness, and those of the people around one.
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, however, that due to the novelty and uncertainty surrounding one’s confrontation with death, experiencing anxiety is perfectly natural. That said, there is an important distinction to be made between commonly experienced end-of-life anxiety in its various manifestations, and devastatingly pathological end-of-life anxiety.
Regardless of its severity, end-of-life anxiety requires prompt treatment, and psychedelic-assisted therapy offers promise.
A look at the history of psychedelics for mental wellness, as well as current evidence of psychedelics for treating mental health problems.
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Given the understandably high level of attention that psychedelic compounds attract, it can be easy to think of psychedelic-assisted therapies as mere drug treatments. However, important distinctions exist between psychedelic-assisted therapies and 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 engendering sustained changes in brain connectivity. Unfortunately, clinical trials have shown that these medications are just marginally more effective than placebo, if at all, may take several weeks or months to exert their effects and often come with a plethora of nasty side effects.
Psychedelics, on the other hand, are typically administered just once or in a series of 2-3 times, in a comfortable, aesthetic living room-like environment, and in conjunction with non-directive, supportive psychotherapy delivered before, during, and after sessions.
Unlike antidepressants, psychedelics alter one’s neurophysiology for short periods, yet they seem to produce rapid, robust, and sustained improvements in psychological well-being.
Why might this be? Researchers acknowledge that how psychedelics reduce one’s death anxiety has yet to be established. However, we do know that when faced with death, our ego or sense of subjective self-identity becomes threatened. High doses of psychedelics seem to counter this anxiety-inducing threat through their reliable occasioning of mystical-type experiences, in which one’s sense of self is severely compromised or indeed even completely dissolved.
Ego-dissolution is often accompanied by a profound sense of being a part of something bigger than oneself, of universal interconnectedness, and an ineffable noetic quality that transcends the physical realm. Such an experience can be incredibly transformative and healing for anyone suffering from end-of-life anxiety. These powerful effects can help patients to reframe their perception of self in a more positive way, allowing them to reconcile with death and achieve an emotional separation from their illness.
In January of 2011, Jama Psychiatry published a study entitled ‘Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer’, which, according to the study’s authors, was conceived to determine whether psilocybin could ameliorate the anxiety associated with their advanced-stage cancer.
Led by Dr. Charles Grob, revered 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 their psilocybin sessions, many patients experienced broad-spectrum psychedelic effects, including positive derealization, positive depersonalization, altered sense of time, positive mood, and synesthesia, which, supported by treatment team personnel, produced substantial decreases in end-of-life anxiety which were sustained for at least 6 months.
Following this, Johns Hopkins researchers at the Center for Consciousness and Psychedelic Research, led by consummate professor of psychiatry and neuroscience, Dr. Roland Griffiths, conducted a randomized double-blind trial that involved 50 patients with a life-threatening cancer diagnosis and comorbid anxiety and/or mood symptoms. Griffiths and colleagues compared two doses of psilocybin, one high (22 or 30 mg/70 kg) and one low (1 or 3 mg/70 kg), which patients received in identically appearing capsules.
Lending support to Grob and colleagues' earlier demonstration of psilocybin’s anxiolytic potential, one high-dose psilocybin session produced large decreases in clinician- and self-rated measures of anxiety in 76% of participants. These improvements were sustained, with 83% of participants continuing to show clinically significant reductions in anxiety 6 months later.
In addition to producing significant decreases in anxiety, psilocybin-assisted therapy was observed to:
Around the same time, New York University researchers conducted a double-blind, placebo-controlled, crossover trial involving 29 patients with cancer-related anxiety. In this study, a single-dose psilocybin (0.3 mg/kg) produced clinically significant reductions in end-of-life anxiety in 60-80% of participants, decreasing demoralization, hopelessness, and existential distress, as well as improving spiritual well-being, quality of life, and attitudes toward death.
Strikingly, 57% of participants continued to demonstrate clinically significant reductions in anxiety between three and a half and five and a half years later, with 71–100% rating their psilocybin experience among the most personally meaningful and spiritually significant experiences of their lives.
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 studies from the 70s, LSD produced a significant reduction in end-of-life anxiety as experienced daily. Similar to Dr. Charles Grob’s 2011 study with psilocybin, the more stable tendency to attend to, experience, and report anxiety (trait anxiety) showed a compelling 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 demonstrate powerful therapeutic effects.
Having recently gained widespread attention for its seemingly remarkable efficacy in the treatment of PTSD, as demonstrated in the Multidisciplinary Association for Psychedelic Studies (MAPS) phase 3 clinical trials, MDMA-assisted psychotherapy may also be an effective treatment for moderate to severe end-of-life anxiety and other psychological distress related to life-threatening illnesses.
The primary analysis of a recent double-blind study showed that participants who received 125 mg of MDMA ( followed by an optional supplemental dose of 62.5 mg 90–150 minutes after the initial dose) as a therapeutic adjunct achieved greater reductions in anxiety compared to those in the placebo (125 mg of lactose) group. MDMA-assisted psychotherapy also improved 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.
A group of German researchers recently conducted a pilot study in which they 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
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 very useful multi-functional palliative care treatment.
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.
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.
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.
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.
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.
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.
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 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.
While shrooms were initially used for ceremonial purposes and spiritual awakenings, they have gained popularity for recreational use and current research on shrooms effects in a therapeutic setting is promising.
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.