Psychedelics have long been stigmatized due to an association with the counterculture movement of the 1960s and subsequent resistance to societal expectations. The close connection between the drugs themselves and the negative behaviors people perceive them to produce has resulted in a long hiatus in research for this area.  

If someone were to propose a new mechanism for treating cancer or easing the symptoms of terminal illnesses, I would imagine there would be little hesitation. However, when this treatment involves psychedelics, there is instantly a negative connotation surrounding these practices. The strong opposition to psychedelics being used in modern culture has inhibited proper research and advances in the field of therapeutic psychedelics. More recently, scientists have been able to uncover the benefits of these stigmatized drugs, which provides hope for offering relief to people with treatment-resistant mental illnesses as well as those experiencing anxiety and depression related to a terminal illness. 

While finding treatments for cancer and other terminal illnesses is clearly a priority, it is also very important to find ways to improve the quality of life for those who lack treatment options, such as those who opt for palliative care. There has not been much success in pharmacologic interventions for treating the existential distress resulting from terminal illness and, thus, this is an area of research that has potential for improvement. The feelings of hopelessness and powerlessness that accompany this distress can decrease someone’s will to live, which can have a negative influence on their ability to adhere to treatments, leading to increased mortality rates (Reiche et al., 2017). 

Psychedelics often produce a mystical experience with a noetic quality, or an ultimate reality that transcends space and time (Rosenbaum et al., 2019). Additionally, these experiences often involve confronting the idea of death and one’s mortality (Moreton et al., 2019). This can lead to “ego dissolution” or “ego death,” where one’s sense of self “dies”. Therefore, psychedelics can act as a type of exposure therapy because patients are exposed to a death experience, thereby reducing the fear of their own actual death. This experience also takes the focus away from oneself to instead make connections to a higher purpose. It mimics the reduced fear of death that often results from a near-death experience. These both can lead a person to believe that their death is not necessarily the end of the self (Moreton et al., 2019).

The mechanism by which psychedelics change brain chemistry is by acting as a serotonin receptor agonist. This disrupts the systems of the brain involved in cognition, perception, and emotion (Moreton et al., 2019). Psychedelics reduce the default mode network (DMN) activity and increase the DMN networks that are connected to processing information from the outside world. This leads to an overall decreased connectivity within the DMN but an increased connectivity between brain networks that are usually unrelated (Moreton et al., 2019). It essentially rewires the connections in the brain to initiate changes in perception and cognition that lead a person to direct their concerns away from themselves and instead associate with a greater sense of purpose. 

Psychedelics differ from typical treatments of mental illnesses, as they are not targeting a specific chemical imbalance in the brain, but rather giving an opportunity to satisfy fundamental human needs and facilitate existential confrontations (Moreton et al., 2019). Many psychiatric medications, including selective serotonin reuptake inhibitors, do not offer permanent therapeutic benefits and result in withdrawal symptoms upon the discontinuation of these medications. Therefore, this may not be the best treatment option, especially for someone who is already trying to cope with a terminal illness. The effects of psychedelics are able to persist long after a person’s experience, which makes it a desirable and efficient drug treatment. 

In addition to psychedelics providing relief to mental health illnesses, tryptamines, lysergamides, and phenethylamines all have different anti-inflammatory mechanisms. Thus, psychedelics have the potential to not only treat the mental illnesses associated with cancer and other terminal illnesses, but also to aid in treating the diseases themselves. Psychedelics act as agonists for the 5-HT (serotonin) receptors and since 5-HT₁ and 5-HT₂ receptors are highly expressed on lymphoid tissues and, thus, involved in processes of the immune system, they exhibit anti-viral and anti-tumor responses and important modulatory effects on inflammation via the neuroendocrine system (Szabo, 2015). 

MDMA is a type of phenylethylamine that produces altered sensations and increased pleasure, hence it being referred to as the “club drug”. It acts as an anti-inflammatory agent by increasing the activity of major immune cells (Szabo, 2015). DMT is a tryptamine that is often used in spiritual rituals and acts as an inducer of anti-tumor cytotoxic activity. This drug also exhibits anti-inflammatory functions by regulating the number of inflammatory cytokines released (Szabo, 2015). LSD, a lysergamide capable of inducing auditory and visual hallucinations, acts on both serotonin and dopamine receptors, which makes it unique compared to other psychedelics that do not assert influence on dopaminergic function. LSD has been linked to inhibiting antibody production and the release of inflammatory cytokines. The dosage of LSD has an impact on its effects, with a higher dosage leading to inhibition of adaptive autoimmune responses, whereas lower doses enhance anti-viral and anti-cancer responses. This promising research suggests a way in which psychedelics could be a treatment for both the mental and physical health of a person with cancer (Szabo, 2015). 

LSD is also a pain-relief treatment and has shown to be more effective and produce longer-lasting effects than opioids (Reiche et al., 2017). An experiment with 22 participants receiving 200-300ug of LSD resulted in 14 participants experiencing positive changes measured by the Emotional Condition Rating Scale, which measures depression, psychological isolation anxiety, difficulty in medical management, fear of death, and preoccupation with pain (Reiche et al., 2017). An additional study of 31 terminal cancer patients who were administered 200-500 ug LSD, identified a pronounced improvement in nine patients and a moderate improvement in 13 patients and a negative effect in two patients (Reiche et al., 2017).

Psilocybin is also a potential target for improving symptoms of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety (Reiche et al., 2017). A clinical trial that examined this link used 0.2mg/kg psilocybin as the active treatment and 250mg niacin as an active placebo. The results yielded statistically significant reductions of State-Trait Anxiety Inventory at one and three months and a 30% reduction in depressive symptoms after one month, measured by the Beck Depression Inventory (Reiche et al., 2017). A similar 12-person study using 200ug of LSD or 20ug of LSD for the active placebo also reported promising results. Prior to the experiment, participants underwent 6-8 drug-free preparatory and follow-up psychotherapy sessions. Due to this being a study for terminally ill patients, only 9 of the 12 participants survived the trial. Six of the nine surviving participants reported increased access to emotions and introspective abilities, while seven patients described reduced anxiety and fear of death and improved quality of life (Reiche et al., 2017). These studies support that psychedelics, when used in a controlled dosage and setting, could offer relief to those with a terminal illness. 

Despite a strong negative connotation surrounding the use of psychedelics due to the association with counterculture, there is robust potential for these drugs to offer therapeutic effects in a variety of forms. Not only do they show promise for easing anxiety and depression related to death, but they may also play a role in the immune system and, thus, influence the development and progression of disease. The limited research in this field is largely due to the intense rejection of these drugs in the 1960s due to their percieved negative effects on behavior. This demonstrates the strong influence that society has on science and the advancement of new treatments for disease. The therapeutic use of psychedelics has been a widespread practice in several cultures throughout history. Therefore, the hesitancy to accept these drugs in modern culture is caused more by a fear that they will result in behaviors that go against societal norms than a fear of the drugs themselves. The battle between society and science will always be present but if this barrier can be surmounted, there is promising science showing the benefits of psychedelics used in medicine. 

References: 

Reiche, Simon, et al. “Serotonergic Hallucinogens in the Treatment of Anxiety and Depression in Patients Suffering from a Life-Threatening Disease: A Systematic Review.” Progress in Neuro-Psychopharmacology and Biological Psychiatry, Elsevier, 22 Sept. 2017, http://www.sciencedirect.com/science/article/pii/S027858461730636X. 

Moreton, Sam G., et al. “Embedding Existential Psychology within Psychedelic Science: Reduced Death Anxiety as a Mediator of the Therapeutic Effects of Psychedelics.” Psychopharmacology, Springer Berlin Heidelberg, 29 Nov. 2019, link.springer.com/article/10.1007/s00213-019-05391-0. 

Rosenbaum, D, et al. “Psychedelics for Psychological and Existential Distress in Palliative and Cancer Care.” Current Oncology (Toronto, Ont.), Multimed Inc., Aug. 2019, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726261/. 

Szabo, Attila. “Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities.” Frontiers, Frontiers, 30 June 2015, http://www.frontiersin.org/articles/10.3389/fimmu.2015.00358/full.