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The “Magic” in the Medicines: The Chemistry & Physiological Effects of Psychedelic Compounds

The “Magic” in the Medicines_The Chemistry & Physiological Effects of Psychedelic Compounds

Psychedelic compounds have fascinated humanity for centuries, but their effects on the human brain - the conduit of consciousness - has been shrouded in mystery and intrigue for the majority of our shared history. In the last two decades, neuroscientific research into these compounds, in particular Ketamine (a pseudo-psychedelic) and Psilocybin (a classical psychedelic), through functional neuroimaging (brain scans which show activity in the brain) has shed light on their physiological effects.

We will explore the intricate world of psychedelic compounds, focusing on these two intriguing molecules, while delving into their chemical makeup and the mechanisms of action that underlie the transcendent experiences they facilitate. While you may come across some seemingly complicated terminology in this article, I will endeavor to clarify these along the way.

The Effects of Ketamine: A Dissociative Anesthetic

The effects of ketamine on the brain and mind

Ketamine is a powerful dissociative anesthetic that was first synthesized by Dr. Calvin Stevens in 1962. Its chemical structure is similar to that of phencyclidine (PCP), but it was synthesized to serve as a safer alternative to PCP. Ketamine is classified as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. In simple terms, it blocks glutamate receptors (which serve as accelerators of activity) in the prefrontal cortex (the logical centre of the mind which also functions to suppress emotions and memories, as well as control impulses) and, thereby, temporarily shuts down the prefrontal cortex.

Basically, ketamine ‘puts brakes on your brakes’.

By doing so, ketamine disrupts the communication between neurons in the prefrontal cortex of the brain, resulting in a dissociative state where perception, thoughts, and consciousness become more fluid and associative: Our suppressed emotions and memories spring forward into awareness, allowing for deep emotional release (catharsis) and the realization of new insights into ourselves.

The Effects of Psilocybin: A Natural Hallucinogen

The effects of psilocybin on the brain and mind

Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as “magic mushrooms”. Psilocybin is chemically converted into psilocin in the body, which is the active compound responsible for its hallucinogenic effects.

The chemical structure of psilocybin is similar to serotonin, a neurotransmitter that regulates emotion, attention, visual perception and memory, amongst many other functions. Psilocybin's resemblance to serotonin allows it to bind to serotonin receptors in the brain, particularly the 5-HT2A receptor. This binding triggers a cascade of neural activity, leading to alterations in perception, mood, and cognition.

Unlike ketamine, which disrupts neural communication, psilocybin enhances it; creating a heightened state of consciousness characterized by vivid visual hallucinations, enhanced emotional experience, and a sense of interconnectedness.

The Key Difference Between the Effects of Psilocybin and Ketamine

While ketamine turns down the volume in the logical centre of the brain (the prefrontal cortex), psilocybin turns up the volume on the emotional centres in the brain. They are different routes to the same emotional symphony in a psychedelic experience.

The Key Similarity Between the Effects of Psilocybin and Ketamine

Despite their distinct chemical actions, both molecules induce changes in the default-mode network (DMN) which is a series of interconnected brain regions involved in episodic memory, self-projection and self-referential processing. The core features of such processing represent thoughts and beliefs about our past, our future, our sense of self (identity), our perceptions of other people and our deep-seated beliefs about the nature of relationships.

It is a ‘task-negative system’ that only activates when cognitive energy is not being absorbed by engagement with a task. As such, the DMN is active when one is ‘doing nothing’ and is our default or resting state. Our DMN is filled with our unconscious beliefs built on our life experiences, such as “I’m not worthy of love’, ‘people won’t love me’, ‘I’ll never succeed’ etc. Some may be positive and others negative, but often they are rigid and unbending.

Psychedelics serve two functions with regard to the DMN that have therapeutic value:
  • First, they reduce interconnections between the DMN & CEN (central executive network in the prefrontal cortex) to stop the prefrontal cortex from repressing beliefs and emotions, thus allowing for deep emotional release.

  • Second, they disrupt the DMN to break rigid thinking patterns to allow us to change our perspectives and become open to learning how to behave differently. By experiencing compassion towards ourselves, we may start to learn to treat ourselves better.

Research indicates that conditions such as depression, social anxiety, OCD, addiction and trauma involve rigid thinking patterns in the DMN that we struggle to break. Psychedelics serve to disrupt those patterns and, when paired with a comprehensive therapeutic framework, such as that offered at EQNMT, we can learn behaviours and relationship skills that can help us build new patterns in our minds to help them ‘stick’.

An Added Benefit

Both compounds also serve to enhance neuroplasticity (malleability and adaptiveness in the brain) for a few days to a few weeks after the psychedelic experience. As such, they aid the mind in becoming receptive to forming new habits, which can be a welcome effect if paired with behavioural change strategies from cutting-edge modern therapies.

In some respects, these compounds serve as an accelerator for the changes we make in traditional therapy. At EQNMT, our treatment philosophy is based on the combination of psychedelic medicine with evidence-based therapy to give everyone the best of both treatments and the best chance at living a more fulfilling life.

Find out more about our evidence-based, psychologist-led psychedelic-assisted therapy programs by visiting our website.

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NOTE: While EQNMT offers psychedelic-assisted therapy and wellness programs, we firmly believe in a holistic approach to wellbeing. As such, we acknowledge that psychedelic-assisted therapy might not be useful to or desired by everyone, and encourage healthcare seekers to consult trusted professionals before starting any new form of treatment. Similarly, we advocate for the safe, legal use of psychedelics in a therapeutic setting, guided and administered by qualified professionals.


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