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Can Psychedelics Set us Free from Depression and Anxiety?

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The Depression & Anxiety Cycle:  Can Psychedelics Set us Free?

Written by Luke DeStefano

In this blog we will explore:

  • Some of the warning signs that you might be stuck in a loop of depression and anxiety.
  • The characteristics and causal factors of depression and anxiety.
  • How depression and anxiety work hand in hand and how the cycle plays out from a neurochemical perspective.
  • Understanding the Default Mode Network (DMN) and how psychedelics may help us break out of the anxiety / depression loop.

No matter how skilled we are at navigating the wild seas of life, no matter how dilligenty we study the map and chart the course, we can still get lost. Obstacles, challenges, and confrontations find us all from time to time.  They come in all forms, some glaringly obvious, others hidden in plain sight.  There are monsters of our culture and monsters of our own design.  If we're not careful, life's challenges can pull us under, disoriented and unable to experience the joy of living.  The vicious cycle of anxiety and depression is one of these pitfalls, and one of increasing importance in our rapidly changing world.

One might not immediately think that anxiety and depression are as closely linked as they are, since they are indeed very different subjective experiences.  Anxiety is that state of hyperarousal, over-vigilance, and even hyperactivity brought on by overstimulation both internal and external. Anxiety disorder, for many, is an overwhelming state of preoccupation and fear that may be abstract, existential, or subjectively "irrational."  While one may understand intellectually that their fears are irrational, they can do very little to subdue them, and often spend most of their days feeling stalked by an invisible predator. 

Depression is anxiety's counterpoint;  feeling numb, uninterested, lethargic, disconnected, or even suicidal. Western psychiatric medicine often treats depression and anxiety disorders as separate mental health conditions, each with their corresponding pharmacological interventions, but when we zoom out we find that they are often two sides of the same coin.

These are some symptoms of co-existing anxiety and depression.

  • Irrational worries or fears that won't go away
  • Physical symptoms, such as fatigue, headaches, rapid heartbeat, labored breathing or abdominal pain
  • Difficulty going to sleep or staying asleep
  • Changes in eating habits - either too much or too little
  • Trouble remembering, making decisions or concentrating
  • Constant feelings of sadness or worthlessness
  • Loss of usual interest in activities or hobbies
  • Feeling often tired and cranky
  • Inability to relax and live in the moment
  • Suffering from panic attacks, including the sense of losing inner control


Anxiety and Depression at the Roots.

Whenever we ask questions like "what causes anxiety,"  it's important to remember that the answers we will find are only as good as the tools we use to discover them.  From a clinical perspective, one might suggest that anxiety is a standard mood disorder, a biological maladaptation of the nervous system, a dysfunction of the human machine easily remedied with the right chemical drugs.  

However, if that same anxious patient takes their mental health disorder to a shaman, they might find a patient whose soul has become fragmented, or maybe the patient is the unconscious host of a parasitic spiritual entity that requires a shamanic extraction with the help of visionary plants like ayahuasca, mushrooms, or peyote.  Whichever lens we choose to gaze through, there are often multiple factors at play.

  • Distress - Mental, emotional, relational, physical
  • Genetic Factors - A 2019 study looked at links between genetic features and anxiety and stress-related disorders.
  • Trauma, especially childhood trauma
  • Social stress and discrimination (racism, sexism, classism, etc). Mental Health America (MHA) notes that, in the United States, Black people and Indigenous People of Color are at much higher risk of race-based traumatic stress injury (RBTS).
  • Caffeine
  • Lack of sleep
  • Heavy metal toxicity
  • Parasites
  • Withholding of one's personal truth

When it comes to understanding the roots of a depressive disorder, we must also be diligent to take a nuanced approach, being mindful of the fact that there can obviously be a number of factors as well, and that the symptom severity of clinical depression is often dependant on many interrelated factors.

  • Environmental - Unhappiness or unfulfillment with one's homelife, relationship or job.  Disconnection from nature, lack of sunlight, mold, etc.
  • Neurobiology - Low production of neurotransmitters like serotonin, GABA, and dopamine.
  • Dietary factors - Vitamin & Mineral deficiencies, high-sugar and processed food diets.
  • Lack of sleep
  • Lack of exercise
  • Lack of purpose or meaning in life
  • Lack of community or positive social interaction
  • Childhood Trauma
  • Seasonal Affective Disorder
  • Substance abuse
  • Genetic factors including epigenetic, ancestral trauma, or a family history of mental illness


This is not an exhaustive list by any means. These are just some of the common factors that play a role in the manifestation of a depressive disorder and/or anxiety symptoms, which is why it's important to remember that most therapeutic approaches - both conventional and alternative - have their merits and their limitations.  A person's entire life situation must be taken into account from a holistic perspective.  It's never just one thing, which is why single-pointed approaches to healing poor mental health are often ineffective.

The Vicious Cycle.

Anxiety and depression move in a vicious cycle that goes something like this:

It starts with anxiety.  The mind begins to obsess on an idea, usually a past event or a worry of the future. Oftentimes the subject at hand isn't something we actually have direct control over, especially in that moment. We begin to feel helpless - thus triggering more anxiety.  We feel like we should be doing something to solve the problem, a problem that grows more urgent with every movement but is too abstract or existential to actually be solved.  

In response to this perceived threat, our body begins to release stress hormones, causing an increase of blood pressure and heart rate, shortness of breath, and an increase in body temperature.  Our vision becomes narrow, our stomach tightens, and what started out as a mere thought pattern is now becoming a very real physical experience, which can evolve into a full blown panic attack.  

As fear intensifies, we lose control of our executive functioning in the neocortex (the part of the brain responsible for decision-making) and we start to realize that we're incapable of resolving the perceived issue. We give up, and thus begins the onset of depressive symptoms.

The nervous system, now exhausted, shuts down. We feel like a failure.  Negative self-talk begins.  We tell ourselves we're worthless and incapable.   We may sleep for excessive periods of time, or just feel numb, apathetic, or in extreme cases, suicidal. Depression symptoms may last days or weeks, but after a while, the voices of anxiety return to draw our attention to all the things we've been ignoring.  The voice grows in urgency until we're jolted back into that heightened state of anxiety again.  And so it goes in this way, in a seemingly endless loop of self-regulation gone awry.  

All the while during this process, the brain is firing the corresponding excitatory and inhibitory neurochemicals that activate or deactivate the nervous systems.  These patterns of neurochemical signals, and the recurring thoughts that go with them, fuse together a network of physical connections in the brain called the Default Mode Network (DMN).  We all have a default mode network, that familiar sense of "I" that exists in all of us characterized by our normal, everyday thoughts and behaviors, but because of the extreme neurochemical intensity that comes along with anxiety and depression, the DMN becomes extra robust in people suffering from this mental health condition.  

How Psychedelics Deactivate the Default Mode Network.

Nature loves patterns.  An orbiting star will circle its mother planet indefinitely until an external influence interrupts its course. Our patterns of thought and behavior are just the same.  When things get into a groove, it takes a significant interruption to break them out.  In the groove of a well-established thought/behavior pattern, the brain actually hard-wires itself with physical neural pathways to support these patterns, literally getting "stuck in its ways."  Thankfully, with the right kind of intervention, we can rewire the brain to create a new default mode.  This is called neuroplasticity, the process of creating new neural pathways, of which psychedelics are proving to be an effective treatment option.

Psychedelics have been shown to greatly diminish activity in the DMN, giving the recipient a massive opportunity to re-write negative thought patterns.  A study by the Imperial College London assessed the impact of psilocybin-assisted therapy on twelve patients with severe depression. Results demonstrated that psilocybin-assisted therapy dramatically reduced their depression for a period of up to three months.

Simon Ruffell, psychiatric doctor and ayahuasca researcher compares psychedelics' impact on the DMN to "defragmenting a computer."

"Brain imaging studies suggest that when psychedelics are absorbed they decrease activity in the default mode network. As a result the sense of self appears to temporarily shut down, and thus ruminations may decrease. The brain states observed show similarities to deep meditative states, in which increased activity occurs in pathways that do not normally communicate. This process has been compared to defragmenting a computer. Following this, it appears that the default mode network becomes more cohesive. We think this could be one of the reasons levels of anxiety and depression appear to reduce."

Another way that psychedelics are so effective in treating anxiety and depression is that they reduce our tendency for what is called "experiential avoidance" which is defined as an attempt at avoiding thoughts, feelings, memories, and other (negative) internal experiences.  Experiential avoidance is another very common effect of an overactive DMN.    

Zeifman, R. J., Wagner, A. C., Watts, R., Kettner, H., Mertens, L. J. and Carhart-Harris, R. L. (2020). Post-psychedelic reductions in experiential avoidance are associated with decreases in depression severity and suicidal ideation. Frontiers in Psychiatry, 11:782

In closing.

Just as the cycles of anxiety and depression rise and fall for millions of people every day, the human story has its own cycles to play out.  Periods of darkness and ages of enlightenment come and go like great tides through the architecture of our civilization.  While there is certainly much confusion in the world today, I believe we are entering an age of great illumination of which psychedelics will play an instrumental role for both public health and our success as a species.  

Nature doesn't waste time, and it's no coincidence that these medicines are showing up when they are.  After nearly 60 years of prohibition, we are just scratching the surface of how psychedelics can expedite our evolution towards a happier, healthier human race - a collaboration of interconnected healing as we remember, again, how powerful we truly are.

Let's Evolve Together.

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