The Neuroscience of Psychedelics

Recently I read an incredible book by Michael Pollan called How to Change Your Mind: The New Science of Psychedelics. It’s split up really nicely into individual chapters on the biology, neuroscience, cultural history and his own personal tale of going from someone who’s never been exposed strong substances to really giving them a shot with an open mind. There’s also a lot said about the pschotheraperic uses of psychedelics in helping patients with accepting death and tackling addiction & depression. I’d strongly recommend reading the book and personally found the chapter on neuroscience really mind blowing, so much so that I thought it’s worth writing notes on and sharing them with others. It’s also worth noting that these notes are 95% copies straight out the book and are not in my own words.

The Biology

The molecules Psilocin, LSD, and 5-MeO-DMT are all types of tryptamines which are found in plants, fungi, and animals where they typically act as signaling molecules between cells.

The most famous tryptamine in the human body is the neurotransmitter serotonin. It binds with a dozen or so different receptors, and these are found not only across many parts of the brain but throughout the body, with a substantial representation in the digestive tract. Depending on the type of receptor in question and its location, serotonin is liable to make very different things happen—sometimes exciting a neuron to fire, other times inhibiting it.

The group of tryptamines we call “the classical psychedelics” have a strong affinity with one particular type of serotonin receptor, called 5-HT2A. Psychedelics resemble serotonin closely enough that they can attach themselves to this receptor site in such a way as to activate it to do various things.

LSD has an even stronger affinity with the 5-HT2A receptor which is “stickier” than serotonin itself, making this an instance where the simulacrum is more convincing, chemically, than the original. The science of serotonin and LSD has been closely intertwined since the 1950s; in fact, it was the discovery that LSD affected consciousness at such infinitesimal doses that helped to advance the new field of neurochemistry in the 1950s, leading to the development of the SSRI antidepressants.

Trying to explain consciousness

What neuroscientists, philosophers and psychologists mean by consciousness is the unmistakable sense we have that we are, or possess, a self that has experiences. Sigmund Freud wrote that “there is nothing of which we are more certain than the feeling of our self, our own ego.” Yet it is difficult to be quite so certain that anyone else possesses consciousness, much less other creatures, because there is no outward physical evidence that consciousness as we experience it exists.

“The hard problem” or the “explanatory gap”: How do you explain mind—the subjective quality of experience—in terms of meat, that is, in terms of the physical structures or chemistry of the brain? The idea that psychedelic drugs might shed some light on the problems of consciousness makes a certain sense. A psychedelic drug is powerful enough to disrupt the system we call normal waking consciousness in ways that may force some of its fundamental properties into view. Someone on a psychedelic remains awake and able to report on what he or she is experiencing in real time.

The Default Mode Network

In 2001 neuroscientists discovered the DMN, the Default Mode Network. The network forms a critical and centrally located hub of brain activity that links parts of the cerebral cortex to deeper (and older) structures involved in memory and emotion.

Scientists noticed that several areas in the brain exhibited heightened activity precisely when their subjects were doing nothing mentally. This was the brain’s “default mode” the network of brain structures that light up with activity when there are no demands on our attention and we have no mental task to perform. Put another way, we had discovered the place where our minds go to wander—to daydream, ruminate, travel in time, reflect on ourselves, and worry.

The default network stands in a kind of seesaw relationship with the attentional networks that wake up whenever the outside world demands our attention; when one is active, the other goes quiet, and vice versa. The default mode is most active when we are engaged in higher-level “metacognitive” processes such as self-reflection, mental time travel, mental constructions (such as the self or ego), moral reasoning, and “theory of mind”—the ability to attribute mental states to others, as when we try to imagine “what it is like” to be someone else.

The default mode network is described as the brain’s “orchestra conductor,” “corporate executive,” or “capital city,” charged with managing and “holding the whole system together.” And with keeping the brain’s unrulier tendencies in check.

The brain consists of several different specialized systems—one for visual processing, another to control motor activity—each doing its own thing. Chaos is averted because all systems are not created equal. Electrical signaling from some brain areas takes precedence over others. At the top of this hierarchy resides the DMN, which acts as an uber-conductor to ensure that the cacophony of competing signals from one system do not interfere with those from another. The default mode network keeps order in a system so complex it might otherwise descend into the anarchy of mental illness.

The achievement of an individual self, a being with a unique past and a trajectory into the future, is one of the glories of human evolution, but it is not without its drawbacks and potential disorders. The price of the sense of an individual identity is a sense of separation from others and nature.

Turning off The Default Mode Network

In studies with psychedelics the steepest drops in default mode network activity correlated with volunteers’ subjective experience of ego dissolution. “I existed only as an idea or concept” one volunteer reported. Another recalled “I didn’t know where I ended and my surroundings began.” The more precipitous the drop-off in blood flow and oxygen consumption in the default network, the more likely a volunteer was to report the loss of a sense of self.

It appears that when activity in the default mode network falls off precipitously, the ego temporarily vanishes, and the usual boundaries we experience between self and world, subject and object, all melt away.

The mystical experience may just be what it feels like when you deactivate the brain’s default mode network. This can be achieved any number of ways: through psychedelics and meditation, but perhaps also by means of certain breathing exercises (like holotropic breathwork), sensory deprivation, fasting, prayer, overwhelming experiences of awe, extreme sports, near-death experiences, and so on.

It happens, taking this particular network offline may give us access to extraordinary states of consciousness - moments of oneness or ecstasy that are no less wondrous for having a physical cause. These and other centers of mental activity are “let off the leash” when the default mode leaves the stage and brain scans show an increase in activity (as reflected by increases in blood flow and oxygen consumption) in several other brain regions, including the limbic regions, under the influence of psychedelics. Material that is unavailable to us during normal waking consciousness now floats to the surface of our awareness, including emotions and memories and, sometimes, long-buried childhood traumas.

Everyday consciousness is a hallucination

The default mode network doesn’t only exert top-down control over material arising from within; it also helps regulate what is let into consciousness from the world outside. It operates as a kind of filter or reducing valve charged with admitting only that measly trickle of information required for us to get through the day. We are forever cutting to the chase, basically, and leaping to conclusions, relying on prior experience to inform current perception.

Our perceptions of the world offer us not a literal transcription of reality but rather a seamless illusion woven from both the data of our senses and the models in our memories. Normal waking consciousness feels perfectly transparent, and yet it is less a window on reality than the product of our imaginations—a kind of controlled hallucination.

How is normal waking consciousness any different from other, seemingly less faithful productions of our imagination - such as dreams or psychotic delusions or psychedelic trips? In fact, all these states of consciousness are imagined: they’re mental constructs that weave together some news of the world with priors of various kinds. In the case of normal waking consciousness, the handshake between the data of our senses and our preconceptions is especially firm because it is subject to a continual process of reality testing.

Your brain on psychedelics

With your DMN knocked offline for a few hours your eager brain tries to make sense of the data rushing in, the brain leaps to erroneous conclusions and sometimes what we call a hallucination results. (The paranoid does much the same thing, ferociously imposing a false narrative on the stream of incoming information.) But in other cases, the reducing valve opens wide to admit lots more information, unedited and sometimes welcome.

People who are colorblind report being able to see certain colors for the first time when on psychedelics and there is research to suggest that people hear music differently under the influence of these drugs. They process the timbre, or coloration, of music more acutely - a dimension of music that conveys emotion.

When confidence in our usual top-down concepts of reality collapses, opening the way for more bottom-up information to get through the filter. When all that sensory information threatens to overwhelm us, the mind furiously generates new concepts (crazy or brilliant, it hardly matters) to make sense of it all and so you might see faces coming out of the rain. That’s the brain doing what the brain does - that is, working to reduce uncertainty by, in effect, telling itself stories.

Suppressing entropy in an aging mind

By adulthood the brain has gotten very good at observing and testing reality and developing reliable predictions about it that optimize our investments of energy (mental and otherwise) and therefore our chances of survival. Uncertainty is a complex brain’s biggest challenge, and predictive coding evolved to help us reduce it. In general, the kind of precooked or conventionalized thinking this adaptation produces serves us well. But only up to a point.

Do we pay a price for the achievement of order and selfhood in the adult human mind? While suppressing entropy (in this context, a synonym for uncertainty) in the brain “serves to promote realism, foresight, careful reflection and an ability to recognize and overcome wishful and paranoid fantasies” at the same time this achievement tends to “constrain cognition” and exert “a limiting or narrowing influence on consciousness.” Research on entropy asks us to conceive of the mind as an uncertainty-reducing machine with a few serious bugs in it.

A better way to suppress uncertainty and entropy in the human brain emerged with the evolution of the default mode network, a brain-regulating system that is absent or undeveloped in lower animals and young children. Along with the default mode network, a coherent sense of self or ego emerges and with that, the human capacity for self-reflection and reason. This new highly evolved mode of cognition is called secondary consciousness. Secondary consciousness pays deference to reality and diligently seeks to represent the world as precisely as possible in order to minimize surprise and uncertainty (i.e. entropy).

At the high-entropy end of the spectrum, there are psychedelic states; infant consciousness; early psychosis; magical thinking; and divergent or creative thinking. At the low-entropy end of the spectrum, there’s narrow or rigid thinking; addiction; obsessive-compulsive disorder; depression; anesthesia; and, finally, coma. The psychological “disorders” at the low-entropy end of the spectrum are not the result of a lack of order in the brain but rather stem from an excess of order. This is perhaps most clearly evident in depression, when the ego turns on itself and uncontrollable introspection gradually shades out reality.

Lubricating cognition with psychedelics

People suffering from a whole range of disorders characterized by excessively rigid patterns of thought - including addiction, obsessions, and eating disorders as well as depression stand to benefit from “the ability of psychedelics to disrupt stereotyped patterns of thought and behavior by disintegrating the patterns of [neural] activity upon which they rest.”

So it may be that some brains could stand to have a little more entropy, not less. This is where psychedelics come in. By quieting the default mode network, these compounds can loosen the ego’s grip on the machinery of the mind, lubricating cognition where before it had been rusted stuck. The grip of an overbearing ego can enforce a rigidity in our thinking that is psychologically destructive. It may be socially and politically destructive too, in that it closes the mind to information and alternative points of view. When the influence of the DMN declines, so does our sense of separateness from our environment.

On Psychedelics the specialized neural networks of the brain such as the default mode network and the visual processing system each become disintegrated while the brain as a whole becomes more integrated as new connections spring up among regions that ordinarily kept mainly to themselves or were linked only via the central hub of the DMN. Put another way, the various networks of the brain became less specialized.

Distinct networks became less distinct under the drug as they communicate more openly with other brain networks. The brain operates with greater flexibility and interconnectedness under hallucinogens. When the memory and emotion centers are allowed to communicate directly with the visual processing centers, it’s possible our wishes and fears, prejudices and emotions, begin to inform what we see. One way to think about this blooming of mental states is that it temporarily boosts the sheer amount of diversity in our mental life.

The effects can be long term

Research on the psychedelic experience show long-term changes in the personality trait of openness raises the possibility that some kind of learning takes place while the brain is rewired and that it might in some way persist. Learning entails the establishment of new neural circuits; these get stronger the more exercise they get. The long-term fate of the novel connections formed during the psychedelic experience—whether they prove durable or evanescent might depend on whether we recall and, in effect, exercise them after the experience ends. This could be as simple as recollecting what we experienced, reinforcing it during the integration process, or using meditation to reenact the altered state of consciousness.

Psychedelic experiences may also facilitate neuroplasticity: it opens a window in which patterns of thought and behavior become more plastic and so easier to change. A high-dose psychedelic experience has the power to “shake the snow globe”, disrupting unhealthy patterns of thought and creating a space of flexibility entropy in which more salubrious patterns and narratives have an opportunity to coalesce as the snow slowly resettles.

One of the most interesting things about a psychedelic experience is that it sharpens one’s sensitivity to one’s own mental states, especially in the days immediately following. The usual seamlessness of consciousness is disturbed in such a way as to make any given state—mind wandering, focused attention, rumination—both more salient and somewhat easier to manipulate.

Psychedelics introduce more noise or entropy into the brain which may shake people out of their usual patterns of thought, lubricate cognition in ways that might enhance well-being, make us more open and boost creativity. Psychedelics could help adults achieve the kind of fluid thinking that is second nature to kids, expanding the space of creative possibility.

As for the unwell, the patients who stand to gain the most are probably those suffering from the kinds of mental disorders characterized by mental rigidity: addiction, depression, obsession. “You get stuck on the same thing, you can’t escape, you become obsessive, perhaps addicted. It seems plausible that the psychedelic experience could help us get out of those states, create an opportunity in which the old stories of who we are might be rewritten.”

The power of Psychedelics to temporarily quieten the default mode network and loosen the grip of the ego may just be simple reset a lot mind needs in an ever changing world.