You may have heard about psychedelics such as LSD, ketamine, and MDMA as recreational drugs, but did you know that they are part of an emerging body of research in the field of Palliative Medicine? Here are five things to know about psychedelics.

Psychedelics have been used in healing rituals for hundreds if not thousands of years in Indigenous societies, but the scientific study of psychedelics for medical purposes has waxed and waned for decades.

In some Indigenous societies, physical sickness is thought to represent an underlying spiritual ailment. With guidance from spiritual leaders, healing rituals involving psychedelics such as psilocybin-containing mushrooms, ayahuasca, ibogaine, and peyote were, and continue to be, administered with the intent to heal people by bringing them closer to the spiritual world.

Despite their common use in some Indigenous cultures, the first appearance of a psychedelic substance in Western medicine did not occur until 1938, when the Swiss chemist Albert Hofmann synthesized lysergic acid diethylamide, more commonly known as LSD – and first ingested it in 1943. In the 1950’s and 60’s, psychedelics were researched in the fields of psychology and psychiatry as an aid to psychotherapy for alcohol dependence and mood disorders.

In the mid-1960’s, psychedelic research slowed. Pharmaceutical companies stopped manufacturing psilocybin and LSD in the face of unfavorable media coverage, President Nixon’s “War on Drugs”, and tighter research regulations. In 1970, the Controlled Substances Act was signed, and many psychedelics were classified as Schedule 1 substances, rendering them widely illegal to manufacture, possess, and distribute. As scientific interest in psychedelics diminished throughout the 1970’s, their importance in hippie counterculture took off, adding another layer of complexity to their role in society and culture.

By the 1990’s, scientists in Switzerland, Germany and the United States renewed their interest in studying psychedelics for medical purposes. Continue reading to understand why.

Psychedelics work on different neurotransmitters in the brain – and each provides a slightly different experience.

The default mode network (DMN) is a group of brain regions associated with self-reflection and introspection and is most active when the mind is “wandering.” As the brain develops over a person’s lifespan, the DMN develops rigid pathways of communication between brain regions, forming the “neurological basis for self” which involves thinking about the future and remembering the past. An overactive DMN can lead to rumination and excessively negative self-reflection, and has been associated with depression, chronic pain, and drug cravings. Psychedelics are thought to decrease activity in the DMN, effectively shutting down negative fixed thought patterns and decreasing ruminations – all of which explains their potential role in treating mental health conditions.

The three major categories of psychedelics include: entheogens (psilocybin, LSD, ayahuasca, peyote, and dimethyltryptamine (DMT)); empathogens (methyl​enedioxy​methamphetamine (MDMA) also known as ecstasy or molly); and dissociatives (ketamine).

Entheogens bind to serotonin receptors in the brain (the same receptors affected by many antidepressants). The term “entheogen” comes from the Greek term “god within.” As such, these substances are thought to aid spiritual development by allowing people to “come into being.” Some patients who have used entheogens describe this experience as a sense of sacredness that offers new psychological insights.

Empathogens cause an increase in “feel-good” neurotransmitters such as serotonin, dopamine, and noradrenaline, and produce experiences of emotional openness and relatedness by generating a state of empathy. Some patients describe feelings of love for others, an extreme sense of belonging in the world, and connectedness to the earth, other people, and creatures. This general elevation of mood is reported to improve quality of life.

Dissociatives block NMDA receptors related to memory and promote detachment from one’s surroundings. Some patients who have used ketamine report losing a sense of time and place during their treatment, and being aware of their surroundings, yet disconnected from their bodies and identities. Patients are able to separate themselves from their physical and emotional pain, thereby experiencing less suffering.  

There have been patient reports of positive mood after treatment with all three types of psychedelics.

Psychedelics differ from standard medical treatments in important ways.

Unlike medications that are administered on a regular schedule, psychedelics can often produce a sustained effect on mood and feelings of well-being after only a single dose. To maximize their potential benefits, it is recommended that patients engage with psychotherapy before and after psychedelic treatment. A typical approach may involve the following:

  1. Screening for contraindications including severe mental illness such as psychotic disorders or bipolar disorder or uncontrolled cardiovascular disease
  2. Multiple pre-treatment counseling sessions
  3. A single dose of psychedelic medication administered in a comfortable, safe session, with trained therapists present throughout the several hours long experience
  4. Multiple post-treatment counseling sessions

Psychedelics offer many potential uses in the field of Palliative Medicine.

Medications currently available for anxiety, depression, and pain can come with burdensome side effects that make them less suitable for some patients with serious illness. In addition, most options don’t work quickly enough and often fail to address the existential distress that patients with life-limiting conditions face.

Many studies suggest that psychedelics have limited, if any, negative side effects and can be helpful for patients with serious illness. Psilocybin is reported to be beneficial in the treatment of a variety of symptoms and disorders, including existential distress at end-of-life, anxiety and depression related to end-stage cancer, major depressive disorder, alcohol and tobacco use disorders, and obsessive-compulsive disorder. LSD has been shown to help alleviate anxiety and existential distress at end-of-life. Ketamine has been used successfully in treatment-resistant depression and refractory pain

For patients with life-limiting illness who are experiencing significant existential distress, anxiety, or depression that has been resistant to standard treatments, psychedelic therapy may be an excellent option. 

For now, psychedelics are mostly used as investigational therapies, but this is likely to change in the near future.

Ketamine is already being used off-label to treat depression in stand-alone ketamine clinics. Palliative care clinicians are prescribing oral and IV ketamine off-label to treat refractory pain.  Clinical trials involving ketamine in the palliative medicine population are ongoing, including a trial looking at combining ketamine and psychotherapy in terminally ill patients.

Other psychedelics, particularly psilocybin, are being used in the context of clinical trials for refractory anxiety, depression, and existential distress. Studies on psychedelic therapy for terminally ill patients are being done in multiple academic centers worldwide.

While other psychedelics are currently illegal in most states, some states are broadening access and in other states, patients are attempting to advocate for ‘Right to Try’ laws to legally gain access to psychedelic therapy for investigational use in real world settings. Leaders in the field of palliative medicine, too, are advocating for expanded access, as they recognize the limitations of currently available treatments in treating the distress that can accompany the end-of-life experience. Prominent palliative medicine physicians see psychedelic therapy as a quick, safe, effective but underutilized treatment modality with the potential to significantly improve their patients’ quality of life in the context of an often-limited prognosis. 

Given the growing literature supporting efficacy of psychedelics and the ongoing advocacy of patients and palliative medicine providers, it is likely that psychedelic therapies will become more mainstream in the near future.