The times most associated with psychedelic use are the peace and love decades of the 60s and 70s; however, these little substances are quickly making a comeback, though not for the reason you may think. No, the hippy lifestyle hasn’t taken over today’s youth and Woodstock 2.0 (this time with more bathrooms!) isn’t on the horizon. Instead, these trippy little compounds appear to be trailblazers in psychiatric treatment, particularly for conditions such as obsessive-compulsive disorder, post-traumatic stress disorder, and depression – last of which has had particularly interesting findings that we will investigate further today.
Psilocybin is the name of a compound found in some species of fungi, specifically mushrooms, colloquially known as “magic mushrooms” due to the psychedelic effects experienced after ingestion.
The chemical structure of psilocybin (how various atoms join to create a specific molecule, much like how parts of a model car are connected) is very similar to that of serotonin, a neurotransmitter found in abundance throughout the nervous system. What is a neurotransmitter, you ask? Simply put, they are chemical messengers that are released in response to certain stimuli detected by your body’s nervous system. When released, they make their way to target cells that are equipped with receptors specific to the neurotransmitter. This is important! Think of the receptor as a lock and the neurotransmitter as the key. If you try to unlock your house with your car key, it won’t work. But, if you put that key in the ignition of your vehicle, you’ll see an obvious effect – the car starts. When the neurotransmitter connects with the proper receptor, an action is triggered (like your car starting).
Serotonin is responsible for a vast array of functions throughout the body, but what we will be focusing on today is the role it plays in mood and emotional regulation. As the structure of psilocybin and serotonin are similar, psilocybin can interact with receptors designed for serotonin, especially the 5-HT2A receptor. The name may be confusing, but all that is necessary to understand is that psilocybin really likes this receptor! In fact, it likes it so much that scientists recognize it as a serotonergic psychedelic.
Okay, that was a lot but stick with me because we’re just getting to the interesting part – the therapeutic potential of psilocybin in treatment-resistant depression!
Treatment-resistant depression (TRD) is used to refer to cases of clinical depression that respond minimally to typical treatment options such as antidepressant medication and counselling; these treatments either have little to no effect or their effects are short-lived to the point of being negligible. In these cases, an alternative form of treatment is necessary. Enter psilocybin!
Researchers conducted a study of 19 participants with diagnosed TRD to investigate the efficacy of psilocybin as a treatment, as well as the therapeutic mechanisms associated with it – that is, how exactly does it work in the brain? Let’s dive in.
In this study, participants consumed two doses of psilocybin one week apart. The first dose (test dose) was 10mg while the second dose (therapeutic dose) was 25mg. It is crucial to note that these participants were first provided with a preparation session facilitated by psychiatrists prior to consuming the psilocybin and were also provided with psychological support through the duration of the session and after.
To visualize the effects, participants underwent fMRI scanning prior to consumption of any psilocybin (to establish a baseline) as well as after consumption of the 25mg dose. Before we go too far, let’s address what exactly fMRI is. It stands for functional magnetic resonance imaging and is type of scan that allows for the visualization of brain activity by measuring blood flow! The greater the activity in a particular area, the greater the blood flow. This is because blood delivers the oxygen needed by the brain to function! If you’ve ever witnessed or experienced a “muscle pump”, you’ll be familiar with this concept. Muscles can appear larger following a hard workout due to the increase in blood flow to those specific areas. The brain works similarly, and fMRI allows us to see the “pump” or increased blood flow in different brain regions to determine which are active during certain activities. In this study, the activity was looking at images of human faces with various expressions (scared, happy, neutral, etc.). This is because researchers wanted to look at activity in the amygdala, a specific part of the brain associated with emotion. Now, remember how we talked about serotonin receptors and the love affair between them and psilocybin? Yep, well these receptors run the show in the amygdala, and it is believed that problems with the circuit that connects the amygdala to the prefrontal cortex (the juicy part of the brain that gives you a personality) are what give rise to psychological disorders such as depression; everything is coming together now, isn’t it?
Now that we know what was done during the study, let’s chat about the results. All 19 participants reported a decrease in depressive symptoms for the first week following treatment and the majority reported that this decrease in symptoms lasted another 3-5 weeks. Six months after treatment, a follow-up was conducted which revealed six participants of the original 19 felt their depressive symptoms were still significantly reduced, supporting the idea that psilocybin could provide long-term, stable antidepressant effects for some patients. Looking at the fMRI scans, researchers found a decrease in functional connectivity (FC; how much activity occurs between distinct brain regions over time) between the amygdala and control regions of the prefrontal cortex; something that is believed to be associated with less rumination among patients. This is a promising result as rumination is a major risk factor for the frequency and intensity of depressive episodes!
These results, in conjunction with previous research which showed an increase in the responsiveness of the amygdala following psilocybin treatment, are believed to be associated with an increase in emotional acceptance and a greater ability to engage with emotions.
Though psychedelic treatment for mental disorders remains in the preliminary stages, it is certainly something to keep an eye on – especially as more legislations worldwide push to improve accessibility to these substances for research purposes. Though these findings are certainly fascinating, please do not go out and try snacking on fungi you find in the forest in hopes of improving your mood, you’ll likely end up blasting from both ends and that would surely be depressing.