Under psychedelics, everything seems very deep. Scientists are beginning to wonder why.
In 1882, sitting at his desk with pen and notebook open, Harvard philosopher William James inhaled a thick cloud of nitrous oxide — today better known as laughing gas, a substance dentists use to anesthetize the mouth.
When the vapors worked on him, they filled his mind with what James called «an extremely exciting sense of metaphysical enlightenment». After the effects of the drugs wore off, however, his brain was filled with something incomprehensible — «a strong sense of meaning in which all thoughts were packed». He called this feeling — «the intelligent quality of mystical experience».
In 1882, sitting at his desk with pen and notebook open, Harvard philosopher William James inhaled a thick cloud of nitrous oxide — today better known as laughing gas, a substance dentists use to anesthetize the mouth.
When the vapors worked on him, they filled his mind with what James called «an extremely exciting sense of metaphysical enlightenment». After the effects of the drugs wore off, however, his brain was filled with something incomprehensible — «a strong sense of meaning in which all thoughts were packed». He called this feeling — «the intelligent quality of mystical experience».
The noetic quality describes the sensation of encountering revelations of the highest order, when the secret processes of your mind and the world are revealed to you. But these encounters, as described by James, have an elusive nature that makes it difficult to understand these processes. And during the 20th century, mainstream psychology moved away from nebulous ideas like «noetic quality» and «meaning» in favor of variables that were more objective and observable.
Until 2006, when a landmark paper by the late Roland Griffiths of Johns Hopkins University indicated that all research into the deep meaning that accompanies intellectual epiphanies was returning to mainstream psychology — this time with psychedelic drugs.
The Griffiths study found that two months after taking psilocybin, the active ingredient in magic mushrooms, 2/3 of 30 volunteers rated a subsequent trip as one of the five most significant events in their lives. Further studies asking the same question, such a rate increased to 87% of the participants surveyed, confirming the curious fact that a group of molecules can reliably deliver on demand what psychiatrist Viktor Frankl called «Man's Search for Meaning».
Until 2006, when a landmark paper by the late Roland Griffiths of Johns Hopkins University indicated that all research into the deep meaning that accompanies intellectual epiphanies was returning to mainstream psychology — this time with psychedelic drugs.
The Griffiths study found that two months after taking psilocybin, the active ingredient in magic mushrooms, 2/3 of 30 volunteers rated a subsequent trip as one of the five most significant events in their lives. Further studies asking the same question, such a rate increased to 87% of the participants surveyed, confirming the curious fact that a group of molecules can reliably deliver on demand what psychiatrist Viktor Frankl called «Man's Search for Meaning».
Despite the past two decades of research documenting the close relationship between psychedelics and meaningful experiences, we still know surprisingly little about what actually happens in the brain when psychedelics enter the brain.
In an article published in Frontiers in Psychology, Patric Plesa and Rotem Petranker noted that even «the best minds in psychedelic research consistently report that psychedelics enhance the subjective sense of meaning without an explicit theory of meaning». It's odd that we lack a mechanical understanding of something so essential to a life well lived. If we understood more about the neural mechanics of these bursts of revelation, might we learn something about how to bring them into our sober lives more often?
The project of developing a mechanistic theory of meaning is beginning to take shape. In the past, scientists have not been able to easily identify how the nervous system senses that very «deep meaning». When mental experience comes, people don't usually connect to neurobiological gizmos (instrumental methods of neurobiological research). But the return of clinical studies of psychedelics makes it easier to provoke these elusive states in the lab, and over the past few years scientists have begun to develop hypotheses about what these drugs can teach us about the neurobiology of meaningfulness.
To limit the study of psychedelics through neurobiology, however, would be to repeat the all too common omission in neurobiology of separating the mind from its social and cultural environment, narrowing the study of psychedelic significance to only what happens inside the skull. Subjective experiences, meaningful or not, are shaped by their larger context, around which many indigenous cultures have built their psychedelic rituals.
In an article published in Frontiers in Psychology, Patric Plesa and Rotem Petranker noted that even «the best minds in psychedelic research consistently report that psychedelics enhance the subjective sense of meaning without an explicit theory of meaning». It's odd that we lack a mechanical understanding of something so essential to a life well lived. If we understood more about the neural mechanics of these bursts of revelation, might we learn something about how to bring them into our sober lives more often?
The project of developing a mechanistic theory of meaning is beginning to take shape. In the past, scientists have not been able to easily identify how the nervous system senses that very «deep meaning». When mental experience comes, people don't usually connect to neurobiological gizmos (instrumental methods of neurobiological research). But the return of clinical studies of psychedelics makes it easier to provoke these elusive states in the lab, and over the past few years scientists have begun to develop hypotheses about what these drugs can teach us about the neurobiology of meaningfulness.
To limit the study of psychedelics through neurobiology, however, would be to repeat the all too common omission in neurobiology of separating the mind from its social and cultural environment, narrowing the study of psychedelic significance to only what happens inside the skull. Subjective experiences, meaningful or not, are shaped by their larger context, around which many indigenous cultures have built their psychedelic rituals.
You cannot simply pave the way to a meaningful life; it requires more than just the accumulation of diverse meaningful experiences. Furthermore, experts suggest that you need a broader architecture, a through-line of goals and values that will provide consistency and purpose to the narrative line of your life as a whole. But studying psychedelics to learn more about the biological underpinnings of meaningful experience can yield many fascinating lessons. Rather than providing compelling answers, psychedelic meaning can reveal profound questions that change the way we act in the world.
«Meaning is valuable not only for therapeutic breakthroughs. It is useful wherever we are looking beyond our normal ways of perceiving and thinking because it helps us discover hidden pathways and possibilities» — said Ido Hartogson, author of Traveling America: Setting, Setting, and the Psychedelic Experience in the Twentieth Century. In other words, meaningful experiences, such as well-designed psychedelic journeys, can expand our search for how to live a meaningful life.
Serotonin receptors are the gateway to psychedelic meaning
Any explanation of how psychedelics are so good at evoking «meaning» must involve the brain's serotonin 2A receptors, small proteins scattered throughout the central nervous system that play a vital role in cognition. Each receptor has a small pocket, similar to a landing zone, where properly shaped molecules can dock. Judging by the name, these receptors normally receive serotonin, a neurotransmitter involved in a wide range of functions, from mood to sleep. But psychedelics mimic the structure of serotonin, giving them access to the receptor.
«Meaning is valuable not only for therapeutic breakthroughs. It is useful wherever we are looking beyond our normal ways of perceiving and thinking because it helps us discover hidden pathways and possibilities» — said Ido Hartogson, author of Traveling America: Setting, Setting, and the Psychedelic Experience in the Twentieth Century. In other words, meaningful experiences, such as well-designed psychedelic journeys, can expand our search for how to live a meaningful life.
Serotonin receptors are the gateway to psychedelic meaning
Any explanation of how psychedelics are so good at evoking «meaning» must involve the brain's serotonin 2A receptors, small proteins scattered throughout the central nervous system that play a vital role in cognition. Each receptor has a small pocket, similar to a landing zone, where properly shaped molecules can dock. Judging by the name, these receptors normally receive serotonin, a neurotransmitter involved in a wide range of functions, from mood to sleep. But psychedelics mimic the structure of serotonin, giving them access to the receptor.
In 2017, Katrin Preller, a neuropsychologist at the University of Zurich, published the first experiment to test the specific contribution of these serotonin receptors to the subjective effects of LSD in humans. Participants listened to three types of music: music they considered meaningless (free jazz, Sun Ra fans), music they had pre-selected as being very meaningful to them, and «neutral» music that was similar to the pre-selected songs but they had never heard before.
They listened to each set three times: once while sober; once while taking LSD, which they said made all three pieces of music more meaningful; and once while taking a combination of LSD and ketanserin, a drug that blocks the serotonin receptor so psychedelic molecules can't dock there. The idea was to see if LSD produced an increased level of significance even though it couldn't interact with the serotonin receptor.
The result? Blocking this receptor completely abolished the subjective effects of LSD; participants could just as easily have been sober. Preller's results helped establish that these receptors are crucial to the quality of thought. No receptor activation, no additional significance.
But explaining psychedelic significance through activation of serotonin receptors is like claiming that turning the ignition key makes the car go. Once receptors are activated, many hidden actions occur that are important for understanding the mechanisms of significance.
The brain network that matters
In psychosis research, when people find meaning in what we consider a meaningless event, experts call it «aberrant significance». This concept can also shed light on the psychedelic experience.
As with psychotic episodes, psychedelic meaning can be found anywhere and everywhere. It no longer depends on an external trigger that a sober mind would also find meaningful, such as the birth of a child. While taking psychedelics, I could stare at tree bark, or dirt, or the back of my eyelids for three hours and feel that I had discovered a hidden order to all phenomena. It seems that it is not the individual things that are filled with meaning, but the perception itself as a whole.
They listened to each set three times: once while sober; once while taking LSD, which they said made all three pieces of music more meaningful; and once while taking a combination of LSD and ketanserin, a drug that blocks the serotonin receptor so psychedelic molecules can't dock there. The idea was to see if LSD produced an increased level of significance even though it couldn't interact with the serotonin receptor.
The result? Blocking this receptor completely abolished the subjective effects of LSD; participants could just as easily have been sober. Preller's results helped establish that these receptors are crucial to the quality of thought. No receptor activation, no additional significance.
But explaining psychedelic significance through activation of serotonin receptors is like claiming that turning the ignition key makes the car go. Once receptors are activated, many hidden actions occur that are important for understanding the mechanisms of significance.
The brain network that matters
In psychosis research, when people find meaning in what we consider a meaningless event, experts call it «aberrant significance». This concept can also shed light on the psychedelic experience.
As with psychotic episodes, psychedelic meaning can be found anywhere and everywhere. It no longer depends on an external trigger that a sober mind would also find meaningful, such as the birth of a child. While taking psychedelics, I could stare at tree bark, or dirt, or the back of my eyelids for three hours and feel that I had discovered a hidden order to all phenomena. It seems that it is not the individual things that are filled with meaning, but the perception itself as a whole.
The psychedelic misattribution of meaning can lead us to find meaning where we don't normally find it, such as in the bark of trees. And this mental sense can make objectively false ideas seem true, as researchers in the lab cleverly discover. The conclusion is clear enough: psychedelic discoveries should be treated with a healthy dose of critical reflection.
However, if we ignore whether psychedelic ideas are true or not, the question remains as to why they seem so significant in the first place. While we don't know of a brain network specifically responsible for meaningfulness, we do have a significance network pretty close to it that helps prepare us for action by prioritizing which stimuli from the environment appeal to us. In other words, the relevance network helps us determine what is important to us in our perceptual landscape among the flood of information that we perceive at any given moment.
It is possible that an irritated significance network could explain why everything that enters psychedelic perception may seem to hold the secrets of the cosmos. Activating the serotonin 2A receptor and disrupting the significance network could make everything seem more meaningful, acting like a neural key that opens what philosopher Aldous Huxley called «the doors of perception». But Plesa and Petranker argue that the picture is incomplete. There is another step that takes us from the brain mechanisms of matter to the sense of meaning: communication.
Connections are a way to derive meaning from significance
Psychedelics are known to disrupt another important group of brain regions: the default mode network (DMN). The DMN is associated with self-referential thinking, such as daydreaming about the moment you win the Olympics, or recalling autobiographical memories, such as winning the Olympics, if you actually won the Olympics. This is the think tank of the narrative self.
However, if we ignore whether psychedelic ideas are true or not, the question remains as to why they seem so significant in the first place. While we don't know of a brain network specifically responsible for meaningfulness, we do have a significance network pretty close to it that helps prepare us for action by prioritizing which stimuli from the environment appeal to us. In other words, the relevance network helps us determine what is important to us in our perceptual landscape among the flood of information that we perceive at any given moment.
It is possible that an irritated significance network could explain why everything that enters psychedelic perception may seem to hold the secrets of the cosmos. Activating the serotonin 2A receptor and disrupting the significance network could make everything seem more meaningful, acting like a neural key that opens what philosopher Aldous Huxley called «the doors of perception». But Plesa and Petranker argue that the picture is incomplete. There is another step that takes us from the brain mechanisms of matter to the sense of meaning: communication.
Connections are a way to derive meaning from significance
Psychedelics are known to disrupt another important group of brain regions: the default mode network (DMN). The DMN is associated with self-referential thinking, such as daydreaming about the moment you win the Olympics, or recalling autobiographical memories, such as winning the Olympics, if you actually won the Olympics. This is the think tank of the narrative self.
Psychedelics decrease activity within the DMN while increasing activity between the DMN and other brain regions. Christopher Timmermann, the neuroscientist who heads the DMT research group at Imperial College London (DMT is a psychedelic drug like LSD or psilocybin), explained to me earlier this year that «parts of the DMN become hyper-connected to the rest of the brain».
Other ways of describing the feeling of this hyper-connectedness might be the «connectedness», «oneness», or «oceanic immensity» that often accompanies high doses of psychedelic experiences. Plesa and Petranker suggest that the synergy between changes in our meaningful network and the increasing connectedness of DMN disturbances may offer a formula underlying meaning, or an explanation of what happens in an engine after the key is turned.
This is where the automobile metaphor fails. The mind is not a machine. No explanation of states of consciousness should ignore the social, cultural, and political threads that are woven into the canvas of experience. Perhaps a broader social prism is needed to reconstruct these pieces into a coherent narrative that expands his view to include not only the brain but also the environment in which they are involved.
Does it make your life meaningful?
Suppose scientists succeeded in mapping the precise neural correlates of psychedelic meaning, and they went further by mapping all possible experiences, as imagined by philosopher Robert Nozick in his thought experiment known as the «experience machine».
The machine can make you feel anything you want to feel. All the while, however, you would be floating in a womb-like tank with electrodes attached to your skull, creating your experience through targeted bursts of electricity.
Other ways of describing the feeling of this hyper-connectedness might be the «connectedness», «oneness», or «oceanic immensity» that often accompanies high doses of psychedelic experiences. Plesa and Petranker suggest that the synergy between changes in our meaningful network and the increasing connectedness of DMN disturbances may offer a formula underlying meaning, or an explanation of what happens in an engine after the key is turned.
This is where the automobile metaphor fails. The mind is not a machine. No explanation of states of consciousness should ignore the social, cultural, and political threads that are woven into the canvas of experience. Perhaps a broader social prism is needed to reconstruct these pieces into a coherent narrative that expands his view to include not only the brain but also the environment in which they are involved.
Does it make your life meaningful?
Suppose scientists succeeded in mapping the precise neural correlates of psychedelic meaning, and they went further by mapping all possible experiences, as imagined by philosopher Robert Nozick in his thought experiment known as the «experience machine».
The machine can make you feel anything you want to feel. All the while, however, you would be floating in a womb-like tank with electrodes attached to your skull, creating your experience through targeted bursts of electricity.
The experience machine can make you feel an incalculable amount of meaning — a smooth cascade of one meaningful experience after another. Plugged into the machine, you wouldn't notice it. But about every two years, Nozick imagined, you emerge, as if briefly awakening from a dream, to choose your experiences for the next two years from a menu.
He saw three main reasons that tend to make people refuse to plug in. First, «we want to do certain things, not just have the experience of doing them». Second, we want to be certain people, not just stale bodies floating in a tank. «Someone floating in a tank is an indeterminate blob» — as he puts it. And third, the machine limits our experience to only what the human mind with some additional electrical stimulation can conjure up, closing us off from encounters with deeper or wider realities, be they the natural world, other people, or beings from other dimensions.
Whatever the reason, his point is that if you imagine such an experience machine and yet decide you don't want to spend your life hooked up to it, you are proving that something is important to you beyond the experience itself. Experience machines are meant to be a cautionary tale, and yet legal ketamine clinics are already halfway through their implementation.
Walk into any of the centers scattered around a place like New York City and you'll see people floating like a womb in weightless chairs, with blindfolds and headphones that isolate them from other people and the outside world.
The conclusion that it is more than experience that matters applies to how we think about the role of meaning supported by psychedelics. It shows that we want to live in ways that generate meaning, not just fill our brains with molecules that make all experience meaningful. Researchers have valiantly tried to define a plurality of meanings that, in addition to meaningful and important experiences, takes into account things like specific aspirations and values that «guide our efforts toward a desired future».
He saw three main reasons that tend to make people refuse to plug in. First, «we want to do certain things, not just have the experience of doing them». Second, we want to be certain people, not just stale bodies floating in a tank. «Someone floating in a tank is an indeterminate blob» — as he puts it. And third, the machine limits our experience to only what the human mind with some additional electrical stimulation can conjure up, closing us off from encounters with deeper or wider realities, be they the natural world, other people, or beings from other dimensions.
Whatever the reason, his point is that if you imagine such an experience machine and yet decide you don't want to spend your life hooked up to it, you are proving that something is important to you beyond the experience itself. Experience machines are meant to be a cautionary tale, and yet legal ketamine clinics are already halfway through their implementation.
Walk into any of the centers scattered around a place like New York City and you'll see people floating like a womb in weightless chairs, with blindfolds and headphones that isolate them from other people and the outside world.
The conclusion that it is more than experience that matters applies to how we think about the role of meaning supported by psychedelics. It shows that we want to live in ways that generate meaning, not just fill our brains with molecules that make all experience meaningful. Researchers have valiantly tried to define a plurality of meanings that, in addition to meaningful and important experiences, takes into account things like specific aspirations and values that «guide our efforts toward a desired future».
Working toward a particular desired future requires action in the world, not just modulation of brain activity. This means that more skillfully addressing the crisis of meaning that afflicts many of us may require efforts that change the matrix of everyday life — for example, allowing workers to negotiate shorter workweeks so that they have a greater say. in the lifestyles they can lead and the meanings they generate.
To be clear: I think legal access to psychedelic therapy, even within the medical model, is good news. But if connection is a crucial part of psychedelic meaning, we might want to reconsider excluding it from the formal containers in which we legalize access. Focusing only on making more connections within a single atomized brain may undermine the amount of meaning that can be created.
One consequence could be the introduction of psychedelic group therapy as a standard practice alongside individual sessions. Or continue decriminalization efforts along with managed access, allowing communities to decide how they want to structure their experiences.
Group therapy should become the norm because it is consistent with the psychedelic mechanism of action. Providing more connection — literally between people — in psychedelic settings can lay the groundwork for a stronger experience of meaning, solidarity and, heck, maybe even the emergence of collective action.
Another finding is the study of psychedelic meaning not only as an ingredient in therapeutic outcomes, but also as a separate variable of interest. Although the so-called psychedelic renaissance has largely been the subject of therapeutic research, the humanities are beginning to formalize their involvement.
The Center for Psychedelic Science at the University of California, Berkeley, and Harvard's Mahindra Center for the Humanities recently announced a joint program to explore «the humanistic and social significance of psychedelics». Christiana Musk, who directs the foundation funding the project, added that the value of psychedelics «is not limited to their biological effects», but extends to both their profound past and potential future involving «cultural development and meaning-making».
Given the centrality of meaning in human life, psychedelics offer a great opportunity to ask new questions or revive ancient questions about one of the most enduring and compelling aspects of humanity. But no matter how meaningful the trip, we come down from all the highs. What remains when the drugs are gone is the everyday world, the setting, the environment and the matrix for ordinary consciousness, the journey that lasts the longest and has the most meaning.
The Center for Psychedelic Science at the University of California, Berkeley, and Harvard's Mahindra Center for the Humanities recently announced a joint program to explore «the humanistic and social significance of psychedelics». Christiana Musk, who directs the foundation funding the project, added that the value of psychedelics «is not limited to their biological effects», but extends to both their profound past and potential future involving «cultural development and meaning-making».
Given the centrality of meaning in human life, psychedelics offer a great opportunity to ask new questions or revive ancient questions about one of the most enduring and compelling aspects of humanity. But no matter how meaningful the trip, we come down from all the highs. What remains when the drugs are gone is the everyday world, the setting, the environment and the matrix for ordinary consciousness, the journey that lasts the longest and has the most meaning.