The term "psychedelic" is derived from the Ancient Greek words "psyche" (meaning "mind") and "delos" (which means "to manifest"), coined by a psychiatrist named Humphrey Osmond in a letter sent to the famous author Aldous Huxley in 1956. Writing about the merits and pitfalls of LSD and mescaline, Osmond came up with the rhyming couplet: “to fathom hell or soar angelic, just take a pinch of psychedelic.”

By this, he meant that certain substances have the potential to expose and activate hidden layers of consciousness, triggering experiences that can range from the diabolical to the sublime. Over half a century later, scientists are finally putting psychedelics under the microscope in an attempt to reveal how they generate these surreal phrenic odysseys.

Losing the Self

Poetic though they may be, outcomes like fathoming hell or soaring angelic are difficult to define scientifically. This is why researchers have developed a tool called the Five-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale to help categorize psychedelic experiences. The scale measures aspects such as “oceanic boundlessness”, a feeling of being indistinct from one’s surroundings, plus a more general loss of the sense of self, referred to as “ego-dissolution”.

Exactly how a psychedelic “pinch” transports one’s consciousness down the 5D-ASC rabbit hole is not yet fully understood, although we do know that it all hinges on a particular type of serotonin receptor called 5-HT2A. Numerous studies have revealed that psychedelics like LSD, psilocybin, and ayahuasca exert their mind-altering effects by activating this receptor, and chemically blocking 5-HT2A binding sites appears to nullify the potency of these substances.

For instance, one study found that giving people LSD caused a blurring of the perceived boundaries between themselves and others, but that this could be avoided by deactivating their 5-HT2A receptors using a compound called ketanserin. Dr Matthew Jonson, professor of psychiatry and behavioral sciences at Johns Hopkins University, told IFLScience that this sense of ego-dissolution is a hallmark of “mystical experiences”, which some researchers believe are key to the healing potential of psychedelics.

“The real tell-tale, or at least the most impressive feature of a mystical experience, is having this notion of oneness where the sense of subject and object break down,” he said. One of the world’s most published scientists on the effects of psychedelics, Johnson went on to explain that this phenomenon occurs when psychedelic drugs “loosen the self-narrative” by temporarily disrupting the neurological blueprint for one’s own identity.

An archetypal reaction to psychedelic drugs, mystical experiences are categorized using the Mystical Experience Questionnaire (MEQ), which measures such things as a “feeling that you experienced eternity or infinity” and “the insight that 'all is One'.” How one little receptor can generate such grandiose shifts in consciousness is something that researchers are slowly beginning to understand.

The Ego In The Brain

Once a compound hits up your 5-HT2As, a psychedelic signature pattern of brain activity begins to emerge – the complexities of which have not yet been fully comprehended. In general terms, Johnson explains that “there are drastic changes to network communication in the brain, and it’s probably the case that these underlie all kinds of experiences, both positive and negative.”

More specifically, the default mode network (DMN), containing numerous structures involved in self-referential processing, has been found to disintegrate under psychedelics, meaning that the connectivity patterns that hold this network together become weakened.

This mechanism was initially revealed in 2016 when researchers published the first brain scans under the effects of LSD, leading to the idea that many aspects of psychedelic experiences, including ego-dissolution, are largely mediated by the DMN. As Johnson explains, “when someone has a greater sense of oneness or ego-loss there is more decoupling of the default mode network, so that seems to be playing some part [in generating these effects].”

“However, a caveat to that is that other drugs like alcohol and amphetamine have also been shown to decouple the default mode network, which introduces a bit of a monkey wrench into the idea that this decoupling is the quintessential or critical feature of a psychedelic,” he says. “There are other changes in brain network synchronization that appear to be involved and I think we need more work in that area to figure out what’s really going on.”

The Entropic Brain

Under psychedelics, the neat patterns of connectivity that hold brain networks in place and keep them distinct from one another break down. Simultaneously, a riotous increase in communication occurs throughout the brain as regions that don’t normally interact suddenly become connected. The resultant neurological mayhem is sometimes referred to as an “entropic” brain state, and is responsible for the dizzying and unpredictable nature of psychedelic trips.

For instance, dropping acid causes the visual cortex to start linking up with other brain regions that normally have nothing to do with vision, which may explain the bizarre visual hallucinations that people often experience while tripping. More specifically, the parahippocampus, which processes autobiographical memories, has been found to communicate with the visual cortex under LSD, possibly causing figments of one’s imagination and memories to dance before one’s eyes.

“There is some evidence that psychedelics increase access to autobiographical memories, so they may make certain unconscious material more readily available to conscious awareness,” says Johnson. Fascinatingly, the LSD-induced increase in communication between the parahippocampus and visual cortex appears to be amplified by music, highlighting the massive role that auditory stimuli play in influencing psychedelic experiences.

Having said that, not all trips involve visuals. The psychedelic compound 5-MeO-DMT, found in the secretions of the Colorado River toad, is said to trigger intense mystical experiences that often lack any visual content whatsoever, instead leaving users with a sense of having entered an existential “void”. Then again, the phenomena generated by these substances tend to vary greatly between individuals, and it’s impossible to say exactly how any given person will be affected by a particular psychedelic drug.

Ultimately, the aesthetic details of psychedelic experiences are wildly unpredictable, making it difficult to pinpoint a defining quality that is common to all trips. If there is a thread that links these experiences, it can be found in the fact that they all arise from an entropic form of cognition which, according to Johnson, “allows for more possibilities by creating a more chaotic, less predictable state of consciousness.”

Is This Reality?

Cerebral chaos may not sound like a particularly useful characteristic, but some researchers believe that the tripping brain actually represents a “higher level of consciousness” than our typical, sober state. By expanding the range of possible configurations of brain activity, these curious drugs may in fact unshackle us from the limits of regular consciousness, thus providing access to novel insights and ideas. They may even enable us to catch a glimpse of objective reality, rather than the filtered and restricted version that our brains conveniently present to us.

“What we experience most of the time is not raw, ground truth reality,” says Johnson. “It’s a billion years of evolution processing reality in a particular way that’s allowed us to survive and reproduce.”

For example, he says that “it’s not necessarily inherent in the universe that one should have a sense of self, or that different things should have their own self-identities. Yet all of our problems and all of our experiences, they’re all derivative of that sense of self.”

By disrupting the neurological scaffolding that holds this notion of individual identity in place, psychedelics allow us to experience the world from a perspective that is less constrained by our natural, self-centered system of consciousness. According to Johnson, the opportunity to step outside of this formatted version of reality is in itself hugely liberating and enlightening.

“You realize that your sense of self is an illusion, or at least the concrete form of it that you’ve gotten used to is just a model that you’ve created,” he says. “That gives you more of a flexibility to move and be less constrained by it.”

Thus, by shining a light on the tricks our consciousness plays on us in order to help us navigate the world, psychedelics may one day be used not only to alleviate mental anguish, but to deepen our appreciation of our own nature. Asked for his assessment of the ultimate potential of these fascinating compounds, Johnson replies: “I think in the biggest picture, beyond the treatment of disorders, they can be used as tools to understand the brain and mind.”

In other words, psychedelics do a pretty good job of living up to the literal translation of their name.