While it seems clear that the modalities of the psychedelic state must be rooted in neuronal pharmacodynamics, explanatory paradigms couched in terms of receptor selectivities, structure/activity relationships, agonist/antagonist interactions, activation of limbic substructures, etc., all somehow fail to do justice to the transcendent, transformative reality that becomes manifest when one actually consumes a psychedelic. – Dennis McKenna


As anyone who reads my research knows, I like to start at places of common ground whenever possible.  This article is no different, as I offer the broadest of overviews on the mechanism of our neural pathways and chemicals that affect their functioning in some way.  I then point out the similarities in religious experience as well as what is commonly reported by those who have experienced, in both clinical situations as well as via personal experiences, the profound shift in consciousness that can occur while under the influence of hallucinogenic or psychedelic substances I will refer to as “entheogens” from here on, as well as the profound shift in consciousness that occurs in naturally-occurring altered states of consciousness such as trance states or deeply meditative ones.

I then present the growing body of evidence (albeit circumstantial) that points to what I feel is the most profound aspect of how science itself is revealing an inescapable fact:  Mystical experiences, whether naturally or chemically induced, have tangible effects that reach far beyond temporary chemical reactions acting on our neural pathways through the bombardment or deprivation of normal channels of communication within the brain and central nervous system.  What seems impossible to prove is tangibly obvious to those who experience these states, and what has been presented so far as reasonable scientific explanations for what actually occurs from a series of chemical reactions has been wholly inadequate. It is not enough to merely discuss the effects of drugs on the body – we must come to understand the effects that these substances have on the mind and the spirit in order to truly comprehend the value of these medicines.


Although there are notable exceptions, most of the main categories of psychoactive compounds commonly referred to as hallucinogens (such as tryptamines, psilocybin, and bufotenine) are remarkably similar in structure to serotonin. Serotonin (5-hydroxytryptamine) is thought to be the chief operator at the main switchboard, responsible for dishing out connections throughout the brain as well as maintaining balance throughout the whole of the neural system.  An analogy I’ve seen in several places now compares serotonin to the brain’s gyroscope.  It makes sure that the flow of neural communication throughout our brain remains within acceptable limits.

Serotonin is a neurotransmitter (like dopamine, norepinephrine, and others) that interprets messages coming to and from the brain via neurons (also called brain cells).  It’s often been referred to as the “happy hormone,” just as endorphins are often called, but its role is far more complex.  Serotonin is certainly related to mood and happiness, but just putting more serotonin in to the brain doesn’t necessarily create happiness.  And, oddly enough, about 80% of serotonin exists primarily in cells in our gut to simply regulate intestinal movements.  (Perhaps this explains why my cat comes running to me in excitement after he’s eaten AND just after he’s used the litter box.)  The other 20% exists in our nervous system and that’s where everything from mood, appetite, sleep, depression, and feelings of joy or well-being also get decided.  It’s also somewhat related to memory and learning, and has been linked to sexual desire and performance as well.

Neurons, or brain cells, receive signals from other neurons through the dendrites.  These signals trigger electric impulses in the neuron which travel down the axon to the synapse.  There, stored neurotransmitter molecules are released in to the synapse where they travel to receptor cells on the dendrites of adjacent neurons.  They fit in to these receptor cells, providing an electric impulse to that neuron, which sends electric impulses to the adjacent neuron, and so forth.  This entire process is virtually instantaneous, moving at the speed of electricity through the entire neural pathway.

This basic example and the image below illustrates how neurons in the brain communicate information to each other and to nerve cells throughout the body:

Neurons, or brain cells, receive signals from other neurons through the dendrites.  These signals trigger electric impulses in the neuron which travel down the axon to the synapse.  There, stored neurotransmitter molecules are released in to the synapse where they travel to receptor cells on the dendrites of adjacent neurons.  They fit in to these receptor cells, providing an electric impulse to that neuron, which sends electric impulses to the next adjacent neuron, and so forth.  This entire process is virtually instantaneous, moving at the speed of electricity through the entire neural pathway.

There are a few other key players I’d like to mention.  One is the dorsal raphe nucleus. Look it up in the internet and you’ll likely find nothing more than a smattering of scientific articles.  It’s the largest nucleus related to serotonin located in a group of nuclei in the midline of the brainstem.  It’s the veritable “head honcho” when it comes to dishing out serotonin to various parts of the forebrain.  The raphe nuclei are intrinsically tied to the central nervous system, and many of the neurons in this group of nuclei are serotonergic.  And, a key place it sends serotonin to is our limbic system.

What is the limbic system, you might ask?

The limbic system is a group of interconnected deep brain structures, common to all mammals.  These are the parts of the mammalian brain considered to be evolutionary ancient; the primitive and primordial parts of our brains, connected to a common mutual human evolutionary past. It’s “a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction” (U.S. National Library of Medicine 2010).

The limbic system is thought to be responsible for both instinctive desires and impulses, such as hunger, arousal, fear, etc, and for the regulation of these impulses.  As an example, if you damage the lining on the amygdala in a male cat, the cat will lose all impulse control and will attempt to mate with anything and everything, including other male cats, ducks, and monkeys!  Damage to the limbic system can also result in things such as extreme over-eating, a complete lack of ability to control the emotions, and so forth.  In short; the limbic system both produces these impulses and regulates them on a sub-cortical level (meaning that the regulation happens automatically and outside of our conscious impulse control, which occurs in the pre-frontal cortex).  The limbic system is also where our memories are created and stored (in the hippocampus), and where hormone cycles are regulated.

So, in other words, a lot of the higher level functioning that differentiates us from most animals and that dictates most of our behaviors and actions begins in the limbic system.

What exactly the limbic system comprises as well as its exact function is still widely debated. When we live in a time when the majority of people believe there’s a scientific explanation for just about everything, all it takes is a cursory look below the surface to realize how many of the most basic questions regarding life, as well as the systems that regulate and decide it, actually remain unanswered.  In fact, our belief in this reality falls apart when we start to observe the world at a quantum level.  But that’s for another article.  For now, let’s continue to make our way to the point.


Now that we’ve got a super basic understanding of the places serotonin travels and how it gets there, let’s use a real world example of this system in action.  Explained in simple terms, let’s say we want to get ourselves a piece of chocolate.  Luckily for us, we happen to have a chocolate bar in a cabinet in our kitchen.  Perhaps an image of the cabinet comes to mind.  Perhaps you remember that the chocolate bar was half-eaten already and you can almost taste it in your mind, as a craving creeps up within you.  As these thoughts are bouncing around your brain, a feedback loop has been created as you examine the space around you.

These messages get sent to the limbic system to check how we feel about that chocolate, they get sent to our memory centers to check for our current location, the pathway to the location, as well as the location itself, and among many other places, they get sent to our motor cortex (responsible for locomotion), which then sends messages to the muscles instructing them to walk towards the place the chocolate bar is.

We walk into the kitchen, open the cabinet, pick up that chocolate bar, and enjoy the rest of it.  Success!

But the events that occurred in order to make this one event happen occur at an astounding rate, simultaneously linking the most ancient parts of our mammalian brains which handle things like hunger, cravings, desire, and motion, to those muscles in our body that need to get us to that chocolate bar.  Throughout this series of events, neurotransmitters, including serotonin, were flooding throughout your neural pathways, connecting the past with the present, matching images stored in the memory centers of the brain and acting upon them, while simultaneously activating those primitive instincts of hunger, pleasure and reward.

The list truly goes on, and all this time I thought I was actually the one in control!

So, for our discussion, the key thing to remember is that even something as simple as getting ourselves that half-eaten chocolate bar flows through and relies on some of the most evolutionarily ancient parts of our brain.  Let’s now imagine what might happen if that flow of serotonin across different parts of the brains was interrupted.  What if we suddenly were unable to match images from our external world with the ones stored elsewhere in the brain since those neural pathways were no longer able to transmit messages to the places they needed to go?

If you can understand this, you’re now getting a clear grasp on the mechanism of hallucinogens: they interrupt this flow of information by bombarding key serotonin receptors, blocking neurotransmitters from receiving external information, either replacing that information with whatever information the hallucinogenic molecules might possess or forcing the brain to rely on its own internal messages.

There’s a general agreement that hallucinogens stimulate the serotonin receptors that are normally the targets for these neurons from the raphe nuclei. Some like to call these “roadblocks” and others like to call them “doorways.”  But, what matters most to me is the measurable effect we can see from this action.


Now that we’re experts on how serotonin charts its path through our brain and central nervous system, it’s time to introduce a critical concept.  First, is the definition of mysticism.  Although difficult to place into a neat little box, a definition I like states; “Belief that union with or absorption into the Deity or the absolute, or the spiritual apprehension of knowledge inaccessible to the intellect, may be attained through contemplation and self-surrender” (Wikipedia).  Another, even simpler definition I liked most of all is found in The Free Dictionary; “Immediate consciousness of the transcendent or ultimate reality or God” (The Free Dictionary).

Why is this such a key point to discuss? The mystical experience is common ground upon which we can continue our discussion.  The above experience is reported in extremely similar forms across all major religions including Christianity, Islam, Hinduism, Buddhism, and just about every other.  The above experience is also reported by a number of those who have experienced Near Death Experiences, as well as many who have been under the influence of an entheogen (or mystogen as I like to personally refer to any substance that can invoke immediate consciousness of the transcendent or ultimate reality or God), or who’ve simply spontaneously experienced religious rapture.

In fact, in a groundbreaking paper by Pahnke called “Drugs and Mysticism,” he does an extraordinary job of characterizing the mystical experience via 9 categories.  I won’t go into the details of each of them here, but the short versions of each are as follows: 1. Experience of undifferentiated unity, 2. Transcendence of space and time, 3. Deeply felt positive mood, 4. sense of sacredness, 5. Objectivity and reality, 6. Paradoxicality, 7. Alleged ineffability, 8. Transiency, 9. Persistent changes in attitude and/or behavior.  The one most relevant for our present discussion is his 9th and last category, which, in Pahnke’s words; “…describes the positive, lasting effects of the experience and the resulting changes in attitude towards self, others,life and toward the mystical experience itself” (Pahnke 1963).

In 1962, an experiment known as ‘The Good Friday Experiment’, or ‘The Marsh Chapel Experiment’,  was executed at Harvard Divinity School by Walter N. Pahnke and Timothy Leary.  The study set out to see whether the consumption of psilocybin would create increased feelings of connectedness with the divine and greater spiritual experience in graduate degree divinity students attending Good Friday service.  Half of the students received psilocybin before the service, and the other half received a dose of niacin, which produces physiological but not psychoactive changes.  Almost all of the members of the experimental group reported profound religious experiences as compared to significantly fewer of the control group. About six months after the study, subjects were asked to fill out a questionnaire in which the completeness with which they had experienced each of Pahnke’s nine categories was measured.  The results can be seen below:

In plain English, what the above table reveals is that subjects who had actually taken the psychedelic (psilocybin) responded with 62% of the maximum score when asked if they had experienced “undifferentiated unity with the Universe”, as opposed to just 7% of the subjects in the control group.  And this Earth-sized lopsided result continues right down the line in all 9 categories (Doblin 1991).

These results are nothing short of stunning.  Yet, somehow these results have been largely ignored by the mainstream communities in both science and religion.  There’s no “perhaps” or “maybe” in these results.  And, no matter what spin is placed on them, they point to a single truth, the truth that is experienced by every spiritual seeker, from the casual Westerner looking to experience what psychedelics and hallucinogens are like, to Tibetan monks skilled in the art of deep meditation, to born-again Christians who have experienced true religious rapture, to shamans deep in the Peruvian jungles, even to myself.

There’s an undeniable commonality to these experiences, proving, if nothing else, that entheogens certainly have the power to evoke an experience that is indiscernible from any other mystical experience.

In fact, when you read this quote, what are your first thoughts?:  “Standing on bare ground — my head bathed by the blithe air and uplifted into infinite space — all mean egotism vanishes.  I become a transparent eyeball; I am nothing; I see all; I am part and parcel of God.”

Or, how about this one?: “When we arrived there, I was totally overwhelmed by spiritual sensations. Every molecule, every cell of the body I was inhabiting started screaming out in ecstasy. Suddenly, with no effort on my part, all of my senses became interchangeable and could perform the activities of any of the others. To my joyous disbelief, I could see with my ears and hear with my nose. I even tasted with my eyes.”

Or, what about this third one?: “Such clarity has left me shattered, left to stand naked before what I now know to be, and what I have been told is.  To now be so utterly awake to the knowledge that we all are already in perfect union with the Universe and its universal message of love, I know, beyond any shadow of a doubt, that I have touched the Hand of the Divine.”

Some might think that all of these people must have been on drugs, but the first is a quote from Ralph Waldo Emerson’s 1836 essay called “Nature”, the second is from Swami Krishnapada’s 1999 book called “The Beggar II: Crying Out for the Mercy”, and the third is from my own journal on the first time I had a spontaneous out of body experience while in a deeply meditative state.  To me, any of those experiences are completely interchangeable with the other.

Why then, has this truth been repeatedly dismissed and brushed under the carpet?  Why are so many researchers so satisfied to dismiss these results out of hand by stating things like; “Your mind floats free, enjoying (or being overwhelmed by) images that no longer come from the physical world alone but from an ‘elsewhere,’ a new origin outside of normal reality.  It’s easy to see why you would feel that messages originate with a divine source, since they aren’t connected to a normal reality and can’t be correlated to the environment your senses tell you is there” as David Porush did in his article “Finding God”? (Porush 1993)

Does Porush really believe it’s that simple and so easily explained away?  What is disturbing to me, though, is that he’s not alone, as is obvious in the blanket Schedule I classification of any substance  perceived as psychedelic or hallucinogenic in our culture.  The complex mechanism of entheogens within the body, which researchers admittedly barely understand, affect places in our brain that we can barely pinpoint, causing a series of actions that we still can’t completely trace or explain, actions that have been repeatedly proven to cause significant and lasting changes in ones perception of life and our place in it as a whole. Researchers feel justified in dismissing this experience as nothing more than a simple series of easily explainable chemical reactions, and lawmakers feel free to outlaw any substance that might invoke this experience.

Am I the only one who sees red flags and smells a rat here?


With mainstream religions vying for position, to suggest that entheogens might have the power to provide humans with a direct pathway to the divine is devastating to any hold on power, whether it’s religious or political. What if humans not only no longer needed the middlemen who have exclusive access to the Divine? What if we all individually discovered that we’re far more than we’ve been led to believe, that we hold the power to direct connection with that Divine within ourselves? What if certain drugs effects are, in fact, to create a bond with the Divine?

When so much energy is spent on trying to belittle, destroy, or debunk something, the basic psychological tenant is that it’s because it reveals a fear or a truth.  Even a cursory look into the history of the Roman Catholic Church shows a clear pattern of the systematic obliteration of entire cultures.  Cultures which were particularly heavily targeted were those which had shamanism and altered states of consciousness as the core of their cultural structures. Diego de Landa (See my “Early Christians’ Crimes Against the Mayans” article for details) is but one example of countless efforts at cultural genocide.

It’s easy to forget that history is written by the conquerors, and the majority of the conquerers were those who belonged (and typically still belong) to the most violent cultures.  As an arbitrary political move, Roman Emperor Constantine converted to Christianity in the 4th century, and in 391 under Theodosius, Christianity became the official state religion of Rome.  These men were incredibly efficient at eradicating any beliefs they felt interfered with their morality and unity.  So, cults and cultures that had rites and rituals that were alien or feared by the Romans were simply destroyed.  This persecution reached a fevered pitch in the Middle Ages.

So, what’s my point?  My point is that despite the systematic extermination of the rites, rituals, and culture of shamanism, it remains, and is experiencing a resurgence as awareness of things like Ayahuasca reach the mainstream, mostly thanks to the power of the internet.  Shamanism is a universal phenomena, and exists wherever there are psychoactive plants. Oddly enough, psychoactive plants, specifically entheogens, exist throughout most of the world.  Yet this key fact is widely ignored, and most of the plants, if not demonized, have been simply outlawed.


We live together, we act on, and react to, one another; but always and in all circumstances we are by ourselves. The martyrs go hand in hand into the arena; they are crucified alone. Embraced, the lovers desperately try to fuse their insulated ecstasies into a single self-transcendence; in vain. By its very nature every embodied spirit is doomed to suffer and enjoy in solitude. Sensations, feelings, insights, fancies””all these are private and, except through symbols and at second hand, incommunicable. We can pool information about experiences, but never the experiences themselves. From family to nation, every human group is a society of island universes. – Aldous Huxley

It’s my firm belief that shamanism arose naturally and logically in early humans.  For me and countless others, a single experience with a Plant Teacher completely changed my version of reality, and without question, connected me with something far more than tricks of the molecules I ingested simply interrupting the normal flow of serotonin within me.  With all of the stimuli and different input of the modern world, and what I’ve “seen” while deep in a shamanic trance is more amazingly beautiful and terrifying than I could ever hope to explain, I can’t imagine what it must have been like for early humans who watched the sun cross the sky and the moon and stars appear at night.

There may be no way to ever “prove” beyond any shadow of a doubt that what goes on during shamanic trances or psychedelic experiences is anything more than a series of chemical reactions, but there’s simply no way to prove that those experiences aren’t the pathway to the Divine either.  So many researchers reduce the vividness of the psychedelic experience to chemical reactions because some claim that they can replicate the experience by stimulating certain parts of the brain.  But every one of those artificial experiences I’ve read about pale in comparison to the articulate vividness of a true shamanic trance or psychedelic experience.

I know beyond any shadow of a doubt that entheogens, plant teachers, psychedelics, hallucinogens, or whatever anyone wants to call them, have allowed me to not only touch the hand of the Divine, but it allowed me to remember who I was before I entered this frame.  I so often wish that anyone who does research into psychedelics, especially those trying to debunk to reduce the experience, simply be required to work with a shaman and a chosen plant teacher long enough to experience the classical mystical state that has been shown to be no different than religious rapture.  Perchance, as usual, to dream.

 – Keith Cleversley


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