Grey Matter Episode 3: The Brain Part 1: Psilocybin and Existential Distress

“The Brain Part 1: Psilocybin and Existential Distress”
by Kaitlin Puccio

After the explosion of psychedelic drug use in the 1960s, then-President Richard Nixon approved the Controlled Substances Act, which made the use of such drugs illegal. At this time, and for decades after until the early 2000s, research on psychedelics was effectively halted. By 2017, at around the same time that researchers developed new brain stimulation technology to treat individuals with certain mental disorders, psychedelic research reemerged on a grand scale. With the arrival of this new biotechnology and a renewed focus on psychedelics, 2017 was a turning point for neuroscientists and psychiatrists in the development of trauma treatments. Since then, psychedelic research has made its way into the mainstream conversation by virtue of its ubiquity. In 105 registered clinical trials surrounding psychedelics conducted from 2007 to 2020, 77.1% of studies commenced in 2017 or later.

Psilocybin, the active compound in mushrooms, seemingly works by reducing the effect of memory on perception. That is, most of what we perceive or see in the world is memory. If we look at a tree, the tree is not a new concept. It’s a tree. We can’t not see that it’s a tree. The concept of tree is a memory that automatically attaches to the tree that we see. Psychedelics, in part, remove this memory from perception —the memory being an inhibition to pure perception—so that an individual is left in a complex world with no preexisting concepts—or memories—to cloud the pure perception of that world.

Another psychedelic drug, methyl​enedioxy​methamphetamine (MDMA), seems to work differently, which is perhaps why it is not considered a “classic psychedelic.” MDMA appears to blunt the automatic, memorized—as in, the concept memory—reaction to a perceived traumatic event rather than remove the memory from the concepts that make up that event. With MDMA, the concepts—or memories—remain intact, which means that MDMA treatment for Post-Traumatic Stress Disorder (PTSD) works more like brain stimulation treatment. With brain stimulation technology, by keeping the memory intact but extinguishing an overactive fear response in a patient with PTSD, the individual maintains a complete narrative history, but is able to function normally without having overwhelming panic responses to triggers.

In experiments developing brain stimulation technology, researchers exposed mice to a high-pitched sound and a low-pitched sound, neither of which resulted in a fear response. They then administered a mild shock to the mice alongside the high-pitched sound. When the mice were again exposed to the high-pitched sound with no accompanying shock, they exhibited freezing behavior—a fear response common in prey animals that “play dead” as a last-ditch attempt to escape a predator by whom they have been otherwise overcome. The researchers then “erased” the fear memory by weakening the synaptic connection between the sensory cue (high-pitched tone) and the traumatic event (shock).

Fear responses developed as a survival technique in response to dangerous situations. Some fear responses, however, are debilitating. In humans, for example, a war veteran with PTSD may have an overactive fear response to the sound of a car backfiring, which may trigger memories of gunfire. Brain stimulation technology in humans would weaken the connection between the nerve cells involved in forming this memory, resulting in a normalized response to the auditory signal.

Psilocybin as a treatment for mental disorders like PTSD has become far more widely recognized in the general public than brain stimulation technology, perhaps because it seems to be a more “natural”—and likely accessible, both financially and logistically—approach to treatment. Studies indicate that psilocybin can alleviate existential distress in terminal cancer patients and those suffering from PTSD. Further, countless studies have shown that a single psilocybin treatment has a high success rate of producing a long-term positive change in the emotional state of those struggling with clinical depression. Psilocybin also tends to be very well-tolerated and has no significant side effects. Contrast this with conventional treatments like synthetic, chemical antidepressant medications, which have been shown repeatedly to be ineffective in a large number of cases, have adverse side-effects, and are a long-term treatment that leaves individuals vulnerable to relapse.

In 2019, prior to the COVID-19 pandemic, 1 in 8 Americans were taking selective serotonin reuptake inhibitors (SSRIs). There is debate about whether or not these drugs are over-prescribed—that argument stems from the idea that SSRIs don’t in fact work in a majority of cases. Perhaps they are overprescribed in this sense because there is no other available treatment to attempt. Moreover, in 2019, six million people were reported to have been taking SSRIs for a decade or more. It seems that an effective treatment for clinical depression—regardless of severity—would not be one that patients depend upon for decades or more, but one that helps them make a permanent change. While brain stimulation technology may arrive at this outcome, psilocybin works differently on the brain, and may be viewed as preferable by patients that are more willing to allow their mind to be “opened” by lifting the inhibition—or memory—that clouds pure perception rather than suppressing a learned reaction to that memory and keeping the inhibition (memory) intact.

The stigmatization and illegality of psychedelics in the 1960s left individuals who could have benefitted from psilocybin without access to an effective treatment for decades. Today, government regulators continue to operate on legal inertia. If PTSD and clinical depression (from a terminal illness diagnosis or otherwise) could be treated with a single psilocybin experience, any regulatory delay—whether due to leftover stigma or outdated law—in making it available to patients is unconscionable.

A related article entitled “The Stigma of Psychedelics” may be found on my Psychology Today column, From Obscurity.

Copyright © 2023 Kaitlin Puccio