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CHAPTER FIVE THE NEUROSCIENCE Your Brain on Psychedelics WHAT JUST HAPPENED in my brain?

A molecule had launched me on each of these trips, and I returned from my travels intensely curious to learn what the chemistry could tell me about consciousness and what that might reveal about the brain’s relationship to the mind. How do you get from the ingestion of a compound created by a fungus or a toad (or a human chemist) to a novel state of consciousness with the power to change one’s perspective on things, not just during the journey, but long after the molecule has left the body?

Actually, there were three different molecules in question—psilocin, LSD, and 5-MeO-DMT—but even a casual glance at their structures (and I say this as someone who earned a D in high school chemistry) indicates a resemblance. All three molecules are tryptamines. A tryptamine is a type of organic compound (an indole, to be exact) distinguished by the presence of two linked rings, one of them with six atoms and the other with five. Living nature is awash in tryptamines, which show up 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, the chemical name of which is 5-hydroxytryptamine. It is no coincidence that this molecule has a strong family resemblance with the psychedelic molecules.

Serotonin might be famous, as neurotransmitters go, yet much about it remains a mystery. For example, 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. Think of it as a kind of word, the meaning or import of which can change radically depending on the context or even its placement in a sentence.

The group of tryptamines we call “the classical psychedelics” have a strong affinity with one particular type of serotonin receptor, called the 5-HT2A. These receptors are found in large numbers in the human cortex, the outermost, and evolutionarily most recent, layer of the brain. Basically, the 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.

Curiously, LSD has an even stronger affinity with the 5-HT2A receptor—is “stickier”—than serotonin itself, making this an instance where the simulacrum is more convincing, chemically, than the original. This has led some scientists to speculate that the human body must produce some other, more bespoke chemical for the express purpose of activating the 5-HT2A receptor—perhaps an endogenous psychedelic that is released under certain circumstances, perhaps when dreaming. One candidate for that chemical is the psychedelic molecule DMT, which has been found in trace amounts in the pineal gland of rats.

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. But it wasn’t until 1998 that Franz Vollenweider, a Swiss researcher who is one of the pioneers of psychedelic neuroscience, demonstrated that psychedelics like LSD and psilocybin work on the human brain by binding with the 5-HT2A receptors. He did this by giving subjects a drug called ketanserin that blocks the receptor; when he then administered psilocybin, nothing happened.

Yet Vollenweider’s discovery, important as it was, is but a small step on the long (and winding) road from psychedelic chemistry to psychedelic consciousness. The 5-HT2A receptor might be the lock on the door to the mind that those three molecules unlock, but how did that chemical opening lead, ultimately, to what I felt and experienced? To the dissolution of my ego, for example, and the collapse of any distinction between subject and object? Or to the morphing in my mind’s eye of Mary into María Sabina? Put another way, what, if anything, can brain chemistry tell us about the “phenomenology” of the psychedelic experience?

All these questions concern the contents of consciousness, of course, which at least to this point has eluded the tools of neuroscience. By consciousness, I don’t mean simply “being conscious”—the basic sensory awareness creatures have of changes in their environment, which is easy to measure experimentally. In this limited sense, even plants are “conscious,” though it’s doubtful they possess full-blown consciousness. What neuroscientists and 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 thing of which we are most certain is beyond the reach of our science, supposedly our surest way of knowing anything.

This dilemma has left ajar a door through which writers and philosophers have stepped. The classic thought experiment to determine whether another being is in possession of consciousness was proposed by Thomas Nagel, a philosopher, in a famous 1974 paper, “What Is It Like to Be a Bat?” He argued that if “there is something that it is like to be a bat”—if there is any subjective dimension to bat experience—then a bat possesses consciousness. He went on to suggest that this “what it is like” quality may not be reducible to material terms. Ever.

Whether or not Nagel’s right about that is the biggest argument going in the field of consciousness studies. The question at its heart is often referred to as “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 question assumes, as most (but not all) scientists do, that consciousness is a product of brains and that it will eventually be explained as the epiphenomenon of material things like neurons and brain structures, chemicals and communications networks. That would certainly seem to be the most parsimonious hypothesis. Yet it is a long way from being proven, and a number of neuroscientists question whether it ever will be: whether something as elusive as subjective experience—what it feels like to be you—will ever yield to the reductions of science. These scientists and philosophers are sometimes called mysterians, which is not meant as a compliment. Some scientists have raised the possibility that consciousness may pervade the universe, suggesting we think of it the same way we do electromagnetism or gravity, as one of the fundamental building blocks of reality.

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. True, anesthetics disrupt consciousness too, yet because such drugs shut it down, this kind of disturbance yields relatively little data. In contrast, someone on a psychedelic remains awake and able to report on what he or she is experiencing in real time. Nowadays, these subjective reports can be correlated with various measures of brain activity, using several different modes of imaging—tools unavailable to researchers during the first wave of psychedelic research in the 1950s and 1960s.

By deploying these technologies in combination with LSD and psilocybin, a handful of scientists working in both Europe and the United States are opening a new window onto consciousness, and what they are glimpsing through it promises to change our understanding of the links between our brains and our minds.

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