Around 1740, a French doctor named Pierre-Jean du Monchaux described the unusual case of a feverish patient called L.C., who lost consciousness after a bloodletting to treat a fever.

When L.C. came to, “he reported that after having lost all external sensations, he saw such a pure and extreme light that he thought he was in Heaven,” Monchaux wrote. “He remembered this sensation very well, and affirmed that never of all his life had he had a nicer moment.”

When some people come face to face with death, they have these remarkable experiences: A bright light. An out-of-body experience. A feeling of unity, love, and a lessening of the fear of death. While Monchaux’s may be one of the oldest medical descriptions of a near-death experience, or NDE, the phenomenon itself is much older. NDEs have been recorded across time, as far back as the 12th century, and across cultures.

They’re rare, but not overwhelmingly so: 10 to 18 percent of cardiac emergency patients have an NDE, and an estimated 4 to 8 percent of the general population will experience one. Descriptions of NDEs are similar enough to each other that scientists have questionnaires to rate their validity; one of the most well-known is the Greyson NDE Scale, first developed in 1983.

NDEs can be reminiscent of another ineffable state: one caused by taking psychedelic drugs like DMT, ketamine, LSD, and mushrooms. People who experience psychedelic states sometimes use NDEs as a comparison to describe what they’ve gone through. Enzo Tagliazucchi, a neuroscientist studying psychedelics at the Brain and Spine Institute (ICM) in Paris, says that this analogy to death and dying via psychedelics is intriguing, because it means we may be able to use one to learn about the other.

NDEs can provide a portal to the mysteries of human consciousness, or be a tool we could one day harness through drugs in the face of death anxiety or mental illness. Finding which drugs can emulate NDEs will help scientists study them in a lab, since they’re obviously easier to administer in a controlled setting than an actual NDE.

In a new study in Consciousness and Cognition, Tagliazucchi and his colleagues tried to determine which psychedelic drug most closely resembles an NDE. They looked at more than 15,000 reports of experiences with 165 psychoactive substances, compared them to 625 descriptions of NDEs, then used algorithms to detect similarities in the topics mentioned by both groups.

They found that while psychedelics like mushrooms and LSD are up there in how close they mirror NDEs, they didn’t come in first place. Instead, it was ketamine that ranked the highest, followed by the plant Salvia divinorum.

Ketamine has been used for decades as an anesthetic, but it’s also used recreationally, and known for being “dissociative,” Tagliazucchi tells me.

“It can generate a sense of detachment from the body and the self and, at higher doses, a full-blown dissociative experience (‘k-hole’), which shares many features with NDEs, such as the feeling of being outside the boundaries of the body and navigating a vast space, feelings of bliss and euphoria, moving towards a light, presence of an invisible and irreversible threshold, and so on,” he says.

Anecdotally, DMT has often been closely associated with near-death experiences, Tagliazucchi says. The new findings are intriguing because ketamine and DMT work in the brain in different ways: ketamine is glutamatergic, which means it interacts with receptors in the brain called NMDA receptors. DMT, meanwhile, interacts with serotonin receptors. How could they both lead to an NDE-like state?

In August 2018, Christopher Timmermann, a neuroscience PhD candidate at Imperial College London, co-authored a study in Frontiers in Psychology that compared the effects of DMT to NDEs, based on the anecdotal similarities between the two, “including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying,” the paper says.

In the placebo-controlled experiment, Timmermann and his colleagues gave DMT to some healthy volunteers and gave them questionnaires commonly used for people who have had NDEs. They found that there were many common themes between the experiences, like thinking of death and dying, and finding peace and overall pleasantness.

Timmermann tells me that since their study just looked at DMT, rather than comparing experiences of different drugs, Tagliazucchi ’s new findings are “a very nice complement to the work that we've been doing.” Even though it found ketamine was more similar to NDEs, “It doesn't feel like it's contradicting our results,” he says.

It might instead add further to our understanding of how NDEs come to be. One hypothesis for how NDEs work is that they are the result of chemical changes in the brain when a person is confronting death.

Rick Strassman, a professor of psychiatry at the University of New Mexico School of Medicine and author of _DMT: The Spirit Molecul_e, gave research subjects DMT in the 1990s.

He put forth the idea that NDEs might be caused by an endogenous version of DMT (meaning one generated by the human body) that’s released when a person is close to dying, which would explain why taking DMT would produce a similar experience.

Timmermann tells me that endogenous DMT has been found in the human body, in the lungs and in cerebrospinal fluid, but it’s still unclear today whether enough of it is produced to create an NDE. And since Tagliazucchi and his colleagues found that ketamine was the most similar to NDEs, their work “did not support a potential role of DMT in the generation of NDEs, at least not in the sense that NDEs and DMT-induced experiences presented the highest level of similarity,” he tells me.

Endogenous ketamine, meanwhile, has not been found in the human body. It’s not yet apparent that the brain can produce its own version of ketamine. If people can have an NDE just on ketamine, it complicates the theory that endogenous DMT is the sole cause an NDE.

Tagliazucchi says that some people have speculated that there could be ketamine-like molecules and we just haven’t discovered them yet. They wouldn’t be identical to ketamine so much as molecules that interact with the brain in similar ways. Because of where ketamine interacts in the brain, it has some neuroprotective qualities—it can slow down the death of neurons from threats like a lack of oxygen, called hypoxia.

Tagliazucchi tells me another theory behind NDEs: that they occur naturally to protect our brains in periods of extreme stress or danger, and the influx of these protective molecules leads to an NDE as a side effect. “Certain ketamine-like endogenous molecules could be released at critical moments to protect the neurons...thus increasing the likelihood of survival,” he says. “Since these hypothetical molecules—termed ‘endopsychosins’—would act by the same mechanism as ketamine, they would elicit similar subjective effects, being the main factor underlying NDEs.”

Some potential endopsychosins have been found in the brain tissue of pigs, he tells me, and will be a continuing point of research for those investigating if there’s a ketamine-like cause for NDEs, though he stresses that this research is still very preliminary.

Timmermann says that we should understand DMT and ketamine, and all psychedelic drugs, as “perturbational models,” rather than getting too caught up in their differences. Each drug contains molecules that perturb, or affect, the brain in some way. Their methods might vary, but the brain’s response could still be similar—throwing a rock versus a brick into a pool of water will both elicit a splash and ripples.

Timmermann says that he views the near-death experience as a very complicated one, as is the case for many complex states of consciousness. “Many things may be happening at the biological level that can account for these experiences,” he says. “But probably it's very complex, not a single biological or neurochemical model is going to fully account for it.”

Strassman tells me that future research could give ketamine, DMT, or other drugs to people who have previously had NDEs, and ask them to compare their experiences. Or—in a much more difficult experiment—scientists could measure the molecules that are produced during an NDE and see which drug those relate to, or try to block receptors in the brain and see if that prevents NDEs.

Just because the experience of taking ketamine was found to be most closely related to an NDE in this study doesn’t meant we should throw out the other psychedelics. “Each of them has a role to play in understanding how the mind-brain complex is constituted, and each has a role to play in the clinical arena,” Strassman says.

Why should we care at all how NDEs work? They seem to change the patients who experience them. People come back from them less afraid of death, and sometimes more altruistic and concerned about others.

Being able to reliably reconstruct an NDE could help people cope with terminal illnesses—a single dose of psilocybin was found to help people with advanced cancer grapple with their death-related anxiety. Perhaps ketamine, if it more closely simulates an NDE, could prove to be an effective choice as well. And if an NDE can positively affect mental health, could we harness that experience for those who aren’t dying?

There’s good reason to not be flippant with our prescription of NDEs. Timmermann says it’s important to note that not everyone has a wonderful experience with them. Some people find the experience distressing. Given this, knowing the limits and restrictions of NDEs is crucial.

“This could provide practice for the actual death process and reduce death anxiety if the experience could be trained for and steered in a positive direction,” Strassman says. “Of course, the hazard in any such study is that the drug effect is nothing at all like really dying, and when faced with the real thing, one is taken by complete surprise—in this way, one’s death would be ruined by such an experiment.”

Tagliazucchi and Timmermann say that understanding NDEs is also a fundamental part of basic neuroscience research and the study of consciousness: There is some stability across cultures and time about the content of NDEs. Why?

“How come the brain of different patients manages to produce very similar conscious experiences after close encounters with death?” Tagliazucchi says. “If the patients really ‘flatlined’, where did these experiences come from, in the absence of brain activity to support them? NDEs pose very interesting and challenging questions to contemporary neuroscience.”

As we continue to study NDEs, I often wonder about a day when all of the neurobiological mechanisms are known, and we know exactly what’s going on in the brain and why it produces such a powerful experience.

People ascribe spiritual meaning to both NDEs and psychedelic experiences; will that be diminished if we know too much? Based on current knowledge, NDEs are like any other experience, which is that they’re dependent on brain activity to enter our conscious awareness, Tagliazucchi says. But having a biological basis doesn’t mean that NDEs are lacking in spiritual value.

Tagliazucchi says that he thinks what counts as “spiritual” is loosely defined. “For many, a spiritual experience does not imply any violation to the known laws that govern physics and biology,” he says. “The experience just feels transcendent, important and life-changing.”

Or, as Strassman tells me: “In the living world, spirit works through biology.”