The world’s most mysterious psychedelic is already inside your brain

There’s often a threshold for how weird something can sound beyond which most people stop taking it seriously. One of the quickest ways to kill a conversation, for example, is to start telling someone about that strange dream you had. Perhaps an even more surefire way to land on the far side of that threshold is to tell them about your trip on one of the most bizarre, powerful, and under-studied psychedelic drugs: DMT, or, if you speak chemistry, N,N-dimethyltryptamine. Tales of hyperdimensional worlds populated by various intelligent creatures — tiny machine elves eager to teach you the universe’s secrets or giant praying mantises that seem to harvest human emotions — are commonplace in DMT trip reports. Because these trips are so bizarre, even compared to other psychedelics, DMT has largely lived on the fringes of the ongoing revival in psychedelic research and therapy. Ketamine clinics are spawning left and right. MDMA therapy teeters on the brink of government approval. Legal psilocybin centers are set to open across multiple states. But DMT, once called “the nuclear bomb of the psychedelic family” by Harvard psychologist and psychedelic hype-man Timothy Leary, has lagged pretty far behind in mainstream attention and scientific interest. That’s slowly starting to change. “We unashamedly think there’s value here, beyond the weird stuff,” neuroscientist Chris Timmermann, who leads the DMT Research Group at Imperial College London, told me. Like its more conventional psychedelic counterparts, DMT could play a role in psychedelic therapy, offering a new treatment for conditions ranging from depression to cluster headaches — and it could even serve as a kind of rocket fuel for the science of consciousness. The compound naturally occurs in a variety of mammals and plants. “DMT is everywhere,” wrote chemist Alexander Shulgin, who created nearly 200 psychedelics through the late 20th century. Humans have been ingesting a slow-acting form of it for at least a few hundred, and perhaps thousands of years by boiling DMT-containing vines and leaves to make the psychoactive brew ayahuasca. But scientists didn’t figure out how to isolate, extract, and ingest pure DMT on its own until 1956, which branched the drug off from ayahuasca into its own history. If Timothy Leary was the “high priest of LSD” in the 1960s, the eccentric philosopher Terrence McKenna became DMT’s rhapsodic bard a generation later. “My entire expectation of the nature of the world was just being shredded in front of me,” McKenna recalled of his first trip. “All this stuff was just so weird and so alien and so un-English-able that it was a complete shock — I mean, the literal turning inside out of my intellectual universe.” [Image: Terrence McKenna. https://platform.vox.com/wp-content/uploads/sites/2/2024/10/GettyImages-1322408018.jpg?quality=90&strip=all] Like other psychedelics, DMT was pushed underground when President Richard Nixon outlawed it in 1970. Well before today’s psychedelic renaissance, it was research on DMT’s hallucinogenic effects led by psychiatrist Rick Strassman in the early 1990s that marked the first return of legal psychedelic research. In the decades since, other psychedelics have claimed the spotlight, but in the last few years, DMT research has shown hints of a resurgence. The drug’s unique properties may make it both a more convenient therapy and a more powerful tool for studying the mind than its trippy counterparts: While psilocybin or LSD trips run for several hours, a DMT trip winds down after just 20 minutes, and unlike with other psychedelics, users don’t build up a tolerance to DMT that diminishes its impact. DMT’s propensity to construct rich alternate realities in the minds of its users can also help push the study of consciousness into new terrain. The drug puts the mind’s ability to create immersive, convincing models of the world on full display — the very same thing our minds do during ordinary consciousness (and dreams). And if DMT can simulate that process in a quick and controllable way, then studying the mechanics of DMT trips could help us learn more about the construction of our sober minds, too. Still, even with all the world’s research funding and best scientific minds, we may never be able to truly “explain” what happens under the influence of this peculiar molecule — but there’s certainly more to know than we do now. So to the woefully incomplete degree that’s currently possible, here’s the news on DMT as we know it today, in not-quite-all of its curious and under-studied glory. When pure DMT hit the scene Pure DMT was first synthesized in 1931 but was set aside, leaving its effects unknown. It wasn’t until 1956 that the first straight DMT hit was reported. Hungarian pharmacologist Stephen Szára had wanted to study LSD, but upon requesting some from the Swiss Sandoz Laboratories, which had been supplying to psychiatrists in the 1950s, he was denied. Communist governments scared them enough, but communists with acid? That was too risky. No matter, thought Szára. He pored over the existing psychedelic literature, found research identifying DMT as an active ingredient in longstanding psychedelic drinks of the Amazon, extracted it from the Mimosa hostilis plant, and became the first person to describe what happens when you take a hit. [Image: The DMT molecule, in all of its mundane molecular glory https://platform.vox.com/wp-content/uploads/sites/2/2024/10/GettyImages-1417906279.jpg?quality=90&strip=all] From his Budapest laboratory, Szára reported “brilliantly coloured oriental motifs and, later, wonderful scenes altering very rapidly.” Immediately after, he recruited volunteers from his hospital to try the strange drug. In these first DMT trials throughout the late 1950s, participants reported rooms “full of spirits” and “curious objects.” "“DMT is the most efficient reality-switching molecule currently known to exist”" - Andrew Gallimore Rumors of the immensely powerful, conveniently short-lasting psychedelic began to spread through the 1960s counterculture (famously, they were pretty into mind-altering drugs). By 1962, word of DMT reached Timothy Leary, who was then researching psychedelics at Harvard. He ran experiments that applied his idea of carefully crafting the “set and setting” of a trip — focusing on how everything from a room’s lighting to one’s preexisting cultural ideals shape the psychedelic experience — to DMT. Though Leary’s experiments successfully nudged them toward increasingly positive experiences, DMT trips remained indelibly weird and never rose to the level of LSD among the counterculture’s preferred vehicles for exploring altered states of consciousness. When it was outlawed under the 1970 Controlled Substances Act, the modest interest that remained was largely put on ice. The freeze lasted until the early 1990s, when Strassman managed to jump through the heap of regulatory hoops to carry out legal DMT research at the University of New Mexico, making DMT the origin of today’s revival in psychedelic science. He went on to publish a book in 2000 that dubbed DMT “the spirit molecule,” which was later adapted into one of the most-viewed documentaries on Netflix, starring podcaster Joe Rogan. Still, DMT remained concentrated more on podcasts and internet forums than in the medical and therapeutic highways toward mainstream acceptance like MDMA and psilocybin. High-profile psychedelics research — like much of neuroscientist Roland Griffiths’s work at Johns Hopkins or studies funded by the Multidisciplinary Association for Psychedelic Studies (MAPS) — has tended to focus on psilocybin or MDMA. By 2019, the world’s first dedicated academic center for psychedelic science opened at Imperial College London, where Timmermann was finishing up his PhD on the neuroscience of DMT. After advising a few PhD students also working on DMT, he figured, “Let’s make this into a group and focus our energies into understanding [DMT] from a consciousness perspective,” launching the university’s DMT Research Group in 2022. Now, Timmermann said, “there’s definitely traction here. And the way to develop that is by doing good science.” What it’s like to take DMT Now, the fun stuff. Neurobiologist Andrew Gallimore, author of a forthcoming book on the history and science of DMT, Death by Astonishment, has called it “the most efficient reality-switching molecule currently known to exist, almost instantaneously transporting the tripper from the Consensus Reality Space to a bizarre hyperdimensional omniverse teeming with superintelligent entities of every (un)imaginable form and character.” We’ll get to all that, but let’s move slowly. Recreationally, most people smoke DMT either from a pipe or, especially nowadays, a vape pen. The effects kick in within a few seconds, before you can even exhale the first hit. All psychedelic experiences are dose dependent — a gram and a half of dried mushrooms might as well be a different drug than 5 grams — and with DMT in particular, ascending doses lead not just to more intense experiences, but to different kinds altogether. There’s no agreed upon “map” of what psychonauts (self-experimenters who explore altered states of consciousness) call the “DMT space.” Different people slice it up in different ways, with varying degrees of detail. Some taxonomies have six levels, with names like “The Magic Eye Level” and “The Waiting Room.” Others have mapped out four-step ladders. For brevity’s sake, I’m going to zoom out as much as possible and cram the weirdness of DMT trips into three simple categories: low, medium, and high doses. At low doses, the onset of DMT feels similar to other psychedelics. Colors grow more vivid, your body may tingle, the world appears a bit crisper, as though the contrast and saturation have been dialed up. A portentous, ambient sense of meaning begins to set in, what’s been called the “noetic quality” of psychedelic trips. Read more about the mystery of psychedelics * The biggest unknown in psychedelic therapy is not the psychedelics * Why psychedelics produce some of the most meaningful experiences in people’s lives * Psychedelics could treat some of the worst chronic pain in the world Have questions, comments, or ideas? Email me: oshan.jarow@voxmedia.com. At medium doses, that vivid picture of the world begins to dissolve into classically psychedelic imagery: swirling geometric patterns, flashing colors and shapes, and a general deconstruction of ordinary perception into chaos. Your ordinary sense of self, too, while not obliterated or dissolved, will likely begin to lose its familiar anchors in space and time. Then there are high, or “breakthrough,” doses (around 20–30 milligrams and up), where the distinctly DMT-flavored weird stuff starts to happen. The incoherent imagery of a medium dose snaps into a new kind of coherence, reconstructing a very high-definition world, albeit one that looks entirely different from what we’re familiar with. When people talk about exploring other dimensions on DMT, it’s this dose they’re talking about. “If the dose is sufficient … the user bursts through a kind of membrane into an entirely novel domain unlike anything within this universe,” as Gallimore put it. “The most striking feature of this ‘DMT space’ is its structure, often described as ‘hyperdimensional.’” In our normal states of consciousness, human perception tends to see space as flat, even though, ever since Einstein’s theory of relativity, we’ve known that mass bends space and time. Some consciousness researchers believe that on high doses of DMT, perception takes on this kind of curvy geometry. That could help explain why the experiences are so strikingly unusual, and why it’s so hard to describe them back in our sober minds. But since DMT trips only last a few minutes, people often feel that they’re pulled out of the oddly curved DMT worlds right as they begin to find their bearings, or, as we should probably now get into, before they can finish their conversations with the entities. We do need to talk a bit about the DMT entities One of the strangest things about these breakthrough doses are the entities. “I was neither intellectually nor emotionally prepared for the frequency with which contact with beings occurred in our studies, nor the often utterly bizarre nature of these experiences,” Strassman wrote of his DMT experiments in the ’90s. Not everyone meets entities on DMT, but it happens often enough that it seems like more than a random quirk. A 2022 analysis of 10 years worth of trip reports posted on the r/DMT subreddit, totalling 3,778 DMT experiences, 45.5 percent included “entity encounters,” including: deities, aliens, “creature-based entities” like reptilian and insect beings, mythological beings, “machine elves,” and “jesters.” [Image: An artistic rendition of a DMT entity. https://platform.vox.com/wp-content/uploads/sites/2/2024/10/GettyImages-1468272759.gif?quality=90&strip=all] While McKenna, who succeeded Leary as the voice of the psychedelic counterculture, is often credited with spreading the idea and expectation of encountering “self-transforming machine elves” in DMT space, humans have been encountering other seemingly intelligent beings while under the influence of DMT since well before he had his first trip in 1965. One of the hallmarks of ayahuasca is encountering other spirits and beings, so much so that ayahuasca is often personified as “Mother Aya.” Even among the early pure DMT users in Szára’s experiments in the 1950s, people reported seeing “strange creatures, dwarfs or something.” A young physician recalled that “The whole room is filled with spirits.” Another stated, “In front of me are two quiet, sunlit Gods … I think they are welcoming me into this new world.” A whole scientific literature is emerging to document the different kinds of entities people meet in DMT spaces. (And outside of peer review, there’s a debate over whether these entities and alternate dimensions are “real.” Gallimore, for example, has argued for conducting diplomacy with the DMT entities, since we can’t rule out their existence.) Either way, the full-on construction of novel worlds and beings gives scientists an opportunity to study the mind in the midst of one of its most dazzling abilities: creating worlds of experience. “You can track the brain as it’s dissolving the habitual model of the world and generating a novel one that has equal or even deeper feelings of immersion,” Timmerman told me. What DMT could mean for the science of consciousness DMT, along with the other classical psychedelics — psilocybin, LSD, and mescaline — share a primary mechanism of action, binding to the serotonin 2A receptor and scrambling activity across both the brain’s default-mode and salience networks (brain regions responsible for self-referential thinking and helping our brains choose what information is worth paying attention to). DMT also binds to the sigma-1 receptor, which a team of Hungarian researchers recently found helps protect brain cells when they lack oxygen, as in a stroke. At least one neuroscientist thinks that could help explain the whole entities thing. Also like other classical psychedelics, DMT is neither physiologically addictive (though any drug carries abuse potential) nor toxic to the brain (per that sigma-1 research, it could actually be neuroprotective). Still, DMT experiences can be destabilizing. One of the main risks is sometimes called “ontological shock,” where someone’s worldview is undermined in a way that causes lasting distress. One survey of 2,561 DMT users found that more than half who identified as atheists before their DMT trips no longer identified as atheist afterward. There’s nothing wrong with abandoning atheism per se, but upending worldviews should always be handled with care, caution, and available support. That said, upending worldviews in reliable, controlled, and targeted ways could also help advance our understanding of how minds construct worldviews in the first place. So far, though, psychedelics haven’t quite lived up to their promise of revolutionizing the science of consciousness. “The big limitation on the use of psychedelics to understand the mind and brain concerns how difficult it is to isolate components of the psychedelic experience that we’re interested in,” said Timmermann. His hope is that short trips associated with DMT, which can be repeated in quick succession without diminishing in intensity, will prove more easily interpretable to scientists working in lab settings. For example, DMT research is already turning up a curious pattern that hasn’t emerged with other psychedelics. One of the major findings in psychedelic science has been that the entropy — or randomness, complexity, and disorder — of brain activity is a kind of signature of a trip’s intensity. Stronger trips are associated with higher levels of entropy in the brain, all the way to reports of “ego dissolution,” dubbed the “entropic brain” hypothesis by neuroscientist Robin Carhart-Harris. Most psychedelics push our minds from order to disorder. One surprising thing A 2006 study found that two months after taking psilocybin, the active ingredient in magic mushrooms, two-thirds out of 30 volunteers rated their trip as one of the five most meaningful experiences of their lives. Read Vox’s reporting on the science of how psychedelics crank up the dial of meaningful experiences here. DMT fits this mold, up to a point. Low to medium doses show a reduction in the alpha frequency of brain waves (which correspond to relaxed and wakeful states), along with rising entropy, a signature finding of sober brains sinking deeper into a trip. But in high doses of DMT, that trend flips. The self does not disappear. Instead, the self feels largely intact, but transported to alternate worlds reconstructed out of the chaos. The rising entropy gives way to new neural signatures of order. “We’re starting to see the emergence of low-frequency brain waves in the breakthrough state, usually called delta or theta waves,” Timmermann said. “What’s intriguing about them is that these brain waves are very much present when people are asleep and dreaming. And there’s a resonance between dreams and the DMT state, the deconstruction of the assumptions about external waking life and the reconstruction of a novel world of experience.” These “contractions” in brain entropy, as Timmermann called them, tend to happen when his team asks tripping study participants to pay attention to a single, salient feature of their experience, like an entity. “Our perceptual systems are finding a way to make sense out of this chaos,” he said. Researchers hope that probing how DMT deconstructs and reconstructs our experiences of the world can make at least some progress on psychedelic science’s original promise of a major leap in our understanding of consciousness. “Our scientists are interested in how world-modeling actually comes about, and whether something like DMT can simulate that for us,” said Timmermann. That, in turn, can help us understand “how we generate a model of the world in our habitual, daily lives.” Next year, Timmermann’s research group is moving to University College London, where they’ll add DMT’s molecular relative, 5-MeO-DMT (bufo), to their research agenda, which, I kid you not, is considered even stronger than DMT. If DMT can help scientists study how brains model worlds, bufo can show what happens when the brain stops modeling everything altogether and a bare form of consciousness without content remains. “5-MeO-DMT is like the modeler of no-worlds … it’s like a canvas without the paint on it. If we can have that experience, then you can look into the more fundamental, core workings of the mind and brain,” said Timmermann. Together, DMT and bufo could make for a hell of a one-two punch in the future of consciousness science. What the heck is DMT doing in the human body? Another mystery sets DMT apart from just about every other psychedelic: It’s naturally produced by the human body, and no one knows why. Research published in 2019 led by a team at the University of Michigan found that some parts of the mammalian brain can have similar levels of DMT as they do serotonin, a neurotransmitter that regulates a huge variety of important functions, from behavior and mood to memory. When trace amounts of naturally occurring DMT were first found in humans in 1965, scientists speculated that it may underlie mental illness, like schizophrenia. Further research found that DMT might actually mitigate symptoms of psychosis, which tanked that idea pretty quickly. Next, in 1976, it was proposed that DMT might be a neurotransmitter, akin to serotonin and dopamine, that has a functional role in the body. Serotonin is popularly associated with happiness, dopamine with motivation and pleasure — but what the heck would DMT be doing in the neurochemistry of our minds? A 2022 review of the last 60 years of debate over DMT’s function concluded that DMT is likely doing something in the brain. But in the two years since, new research has turned up more questions than answers. It’s tempting to speculate. When Strassman called DMT “the spirit molecule,” he meant it rather literally: Its function in the brain, he argued, is simply to elicit psychological states that we call spiritual. Research published in 2019 showed that levels of DMT in rat brains spike during cardiac arrest, lending some substance to a link between DMT and near-death experiences. But neuroscientist Jimo Borjigin, lead author of that study and considered one of the world’s leading experts on the puzzle of DMT in the human body, put it bluntly: “We know nothing — seriously! — about the role of endogenous DMT.” Mainstreaming DMT For all the far-out ridiculousness of DMT — the curvy geometry, the mischievous but generally benevolent elves, the prospect of hidden dimensions — it could have remarkably practical applications. Studies are beginning to corroborate anecdotes, for example, that DMT could treat cluster headaches, one of the most painful conditions known to humankind. DMT could also offer a few advantages over the current generation of psychedelic therapy treatments that rely on MDMA or psilocybin. The big one is money: Psychedelic therapy is incredibly expensive. A few months of MDMA therapy recently tested in clinical trials cost about $11,537 per patient, nearly half of which came from paying two therapists to stay with each patient for a full eight hours during the MDMA sessions. DMT, since it winds down within 20 minutes, could make for much more affordable treatments. Gallimore and Strassman have proposed the possibility of extending DMT trips via a steady IV drip, keeping levels of DMT in the body elevated and stable much like we do with anesthesia during surgery. Last year, researchers from Imperial College London kept 11 healthy volunteers in the DMT space for an extended period of 30 minutes, demonstrating for the first time that “extended DMT,” or DMTx, works and that the length and intensity of DMT therapy sessions could be customized to patient preferences. “When we speak about precision psychiatry and how to treat individuals according to their specific profiles and needs, a plastic and dynamic psychedelic experience could make things cheaper and more effective,” said Timmermann. DMT has already shown promising results for depression, and clinical trials are underway — and patents being filed — for DMT as an injectable treatment. Extended DMT would be exciting news on the consciousness science front, too. The longer people can stay in the strange worlds of DMT space, the more access that gives scientists and psychonauts alike to one of the mind’s most fascinating tricks: constructing worlds of experience. And even though these worlds may be so alien that many of us might be tempted to write them off, there’s no explanation for our universe, no matter how sober, that isn’t unfathomably weird, as philosopher Eric Schwitzgebel writes in his book, The Weirdness of the World. There’s only “a complex blossoming of bizarre possibilities,” where “something radically contrary to common sense must be true about the fundamental structures of the mind and the world.” Given how DMT seems to shred just about every bit of common sense, perhaps it’ll help turn up some answers. Whether that happens may depend on efforts to rein DMT in from the fringes of psychedelia. Given its ubiquity in nature, there’s plenty to go around. And given its presence in our bodies, we all stand to gain from a better understanding of what it’s doing there and why taking more of it leads to what remains perhaps the most bizarre kinds of experiences humans have yet encountered.