From Ruts to Oceanic Boundlessness: Psychedelics and Depression

Many Latin American cultures have long referred to certain psychoactive plants as “plant teachers.” In addition to being an apt metaphor, this ancient term for psychedelics may also be surprisingly accurate from a scientific perspective. As we will see, psychedelics have the potential to promote learning, creativity and psychological healing long after the acute effects of the drug have worn off. Like a wise mentor or therapist, it’s almost as though psychedelics have the power to “teach” our brains about new ways of seeing the world.

Since the late 1960’s and early ‘70’s, scientific investigation into the therapeutic potential of psychedelics has been severely limited by prohibitive laws worldwide. Some researchers have avoided the problem of acquiring psychedelics by conducting population studies that rely on non-clinical methods like surveys and interviews. Such studies have brought into question the popular belief that using psychedelics increases one’s risk of developing mental illness. These studies have indicated no correlation between psychedelic drug use and a higher incidence of mental illness [15][16]. In a large study conducted in 2013, participants who use psilocybin, LSD, and/or mescaline reported fewer instances of psychological distress than participants who had never used psychedelics [16].

The early 1990’s saw a re-emergence of psychedelic research, with researchers testing the therapeutic potential of psychedelics for a wide range of conditions. Clinical studies of psychedelics as a treatment for depression have shown promising results with psilocybin (the active ingredient in magic mushrooms) [1][2][3][4][5][6], ayahuasca[7][8]and ketamine[9][10][11][12][13][14]. Pre-clinical studies indicate that other psychedelic substances may have similar effects. Unlike conventional antidepressant medications, a single dose of a psychedelic substance such as psilocybin can have an immediate effect on depressive symptoms.

Until recently, chemical abnormalities or “imbalances” in the brain were believed to be a major cause of depression. Depressed people were believed to have lower levels of the brain chemicals known as monoamine neurotransmitters, including serotonin (5-HT). Most antidepressant medications currently on the market target monoamine neurotransmitters. Unfortunately, the so-called monoamine theory of depression hasn’t held up to testing particularly well. Depressed patients do not categorically have lower levels of serotonin or other monoamines, and an increase in monoamine levels alone has not been demonstrated to have any significant effect on the symptoms of depression[17].

In order to understand why psychedelics are considered such a promising potential treatment for depression, it is vital to understand a little bit about how the brain works. Information is relayed from one part of the brain to the next in the form of electrical impulses that travel along specialized nerve cells known as neurons. Neurons are constantly regenerating, forming new connections, and “pruning” old connections that are no longer needed. This is known as neural plasticity. There are billions of neurons in each of our brains. Together, they form an extremely complex living circuit that is being “re-wired” on a constant basis. Thanks to plasticity, everything we experience leaves an impression on the brain. The general consensus among neurologists used to be that the vast majority of neural “rewiring” occurs early in development, during childhood. We now know that the brain can retain high levels of neural plasticity at all stages of life, and that extensive rewiring frequently takes place well after other parts of our bodies have ceased to develop in any significant way.

An increased rate of cerebral atrophy in the prefrontal cortex region of the brain, an area vital for critical thinking and creativity in humans, is considered a major risk factor for depression[18]. Cerebral atrophy denotes both the loss of connections between neurons, and the deterioration and loss of the neurons themselves. Psychedelics have been found to rapidly promote neural plasticity in the prefrontal cortex[19].People who experience depression often describe it as like being in a rut, unable to respond emotionally to the people, places and activities that used to excite them or bring them comfort. It’s possible that the increased neural plasticity afforded by psychedelics may work to alleviate depression by providing depressed patients with an improved ability to change their outlook on life.

Another property of psychedelics that may help explain their effect on depression and other forms of mental illness is their ability to alter something called the “dynamic functional connectivity” of existing functional neural networks. Adjacent areas of the brain that form connections are said to be structurally connected, whereas areas of the brain that become active at the same time as other, spatially remote areas are said to be functionally connected. Dynamic functional connectivity refers to changes in functional connectivity over time. The state of mind achieved with psychedelics is known as a brain-dynamic state, in which the brain can switch between functional connectivity states more quickly than normal. Since people with depression are believed to have more difficulty “shifting gears” between various functional connectivity states than non-depressed people[21], the therapeutic effects of psychedelics may be at least partially due to their ability to promote brain-dynamic states.

One final clue as to why psychedelics help depressed patients is potentially the most intriguing. In a 2018 study, patients with treatment-resistant depression were given a single dose of psilocybin and were asked to rate their subjective experience with self-report scales. A reduction in depressive symptoms five weeks later was correlated with lower levels of anxiety related to one’s subjective loss of ego and higher levels of something researchers call “oceanic boundlessness,” during the psychedelic experience itself[6]. Oceanic boundlessness, which is a real scale developed by psychologists to describe spiritual or “mystical” states of mind, includes four sub-factors: insightfulness, blissful state, experience of unity, and spiritual experience[6]. Some people describe the sensation of oceanic boundlessness as a feeling of being at one with the universe. In other words, it seems that the therapeutic properties of psychedelics go well beyond the purely biochemical. Perhaps it is only by embracing the otherworldliness of the psychedelic experience that we may hope to one day understand all of its mysteries and in the process we just may find an effective treatment for depression.

Image: Karen Jones

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