In 2006, neuroscientist Adrian Owen and his colleagues reported what happened when a woman stuck in an unresponsive state was asked to imagine playing tennis. Her brain showed a pattern of activity nearly identical to a healthy person's. “She wasn’t vegetative at all,” Owen wrote in his book, Into the Gray Zone: A Neuroscientist Explores the Border Between Life and Death. “She was responding to us, doing everything we asked.”

Since the late 1990s, Owen has been looking for signs of hidden consciousness in people largely believed to have none. His patients have disorders of consciousness (DoC), which result from traumatic brain injuries, or other incidents that cut off oxygen from the brain. DoC are different from comas; in vegetative or minimally conscious states, a person is awake, but not aware. Their eyes can be open, they occasionally move, and they have an eerie, almost-there presence.

Owen and others have published work finding that 15 to 17 percent of DoC patients can produce brain responses like the woman playing imaginary tennis. There’s a current push to set up and enforce better guidelines for diagnosing DoC, but a larger problem looms: Even if doctors get better at diagnosing these states, we still lack ways to actually treat them.

A paper published last week in The Neuroscience of Consciousness examined one out-of-the-box proposal from April: giving DoC patients psilocybin, the active ingredient in magic mushrooms, to see if it can restore consciousness in some way.

Andrew Peterson, an assistant professor at the Institute for Philosophy and Public Policy at George Mason University, said his gut reaction was “‘Are you tripping!?’—pun intended.” But later, he felt it was worth consideration.

In the new work, Peterson and his co-author, neuroscientist Enzo Tagliazucchi, applied an ethical model called the Value-Validity Framework to the idea—a way of interrogating if a trial's outcomes would be worth whatever burden it places on the patients. Their paper is neither an endorsement nor a disparagement of the concept, he said. Instead, Peterson hopes it is a roadmap for anyone who wants to conduct research in consciousness.

The idea of giving psilocybin to DoC patients is based on theories around brain complexity and consciousness. Brain complexity is the level to which different regions of the brain communicate with one another, and lower states of awareness are associated with less complexity.

Psychedelics seem to increase levels of complexity beyond what’s normal, said Gregory Scott, a neurologist at Imperial College London and an author of the paper from April. There are multiple examples of a relationship between brain complexity and consciousness, and evidence of increased brain complexity in healthy people given psilocybin, but the link between psilocybin and improvements in consciousness is unresolved. That’s why Scott and his co-author, Robin Carhart-Harris, head of the Psychedelic Research Group at Imperial, proposed such a trial.

“The simple way of framing it is that disorders of consciousness have low complexity, and these drugs seem to increase complexity,” Scott said. “Let’s see what these drugs do in disorders of consciousness. Can they increase complexity and accordingly increase consciousness levels?”

Through a trial, they could measure psilocybin's therapeutic value, and also learn something about consciousness, Scott said. Psilocybin interacts with a particular kind of serotonin receptor, and increases the activity of neurons with a lot of those receptors. Those neurons are concentrated in parts of the brain that have been implicated in consciousness, and seeing how they respond could guide our understanding of just how crucial these areas are.

Scott and Carhart-Harris suggested starting extremely slow, in healthy subjects first, who are either sedated or sleeping, to see how psilocybin affects consciousness and complexity in those states. If those results are promising, and the study design proves to be safe, only then would they move on to patients that have any form of DoC.

No such trial exists yet, and doing any kind of research on people with DoC is ethically fraught. They aren’t able to give consent, or say if what’s being done is hurting them. Psilocybin received a “Breakthrough Therapy” designation from the FDA for trials in treatment-resistant depression, but DoC patients are an entirely different population, often with injured brains and co-morbid illnesses. Just because it's been deemed safe for depressed people doesn't mean it applies to DoC too.

One ethical concern is the self-awareness paradox. While the end goal is to restore consciousness, what if by doing so, you make someone more aware of their situation, their injury, their quality of life, and end up inflicting emotional or physical pain?

There's also a disturbing possibility of a “bad trip." Tagliazucchi said that with assistance, people are able to manage any anxiety that might arise. But since DoC patients cannot communicate, the "bad trip" could occur "in a completely isolated individual, and this is a situation we have never encountered before in our research with healthy participants," Tagliazucchi said.

These outcomes are troubling, but the purpose of Peterson and Tagliazucchi's new paper is to consider the ethics as we should any other intervention. Do psychedelics raise any ethical issues that are unique? "Not necessarily," Peterson said. "Psychedelics are just one kind of new drug that could (or could not) be effective for this clinical purpose," Peterson said. (They also point out that more invasive measures like deep brain stimulation are already being tried on these patients—is that ethical?)

Just because a population desperately needs options doesn't mean that researchers should try anything, Owen said. But he thinks a hesitation toward psychedelics shouldn't stop people from considering it, and that it's worth a carefully designed, safe trial. After all, when he first started to study consciousness in vegetative patients, people thought that was a waste of time and resources. “If we’d succumbed to those ‘knee-jerk’ early reactions, 20 years of extremely valuable science would never have occurred,” he said.

Scott feels that doing nothing isn't the most ethical option, especially as the number of people who end up in these states increases. People who suffer traumatic brain injuries, or heart attacks during which their brains are deprived of oxygen are more likely to survive given the improvement in acute medicine.

“It’s potentially the case that we're generating more people who are in this state because those people would have died 20 to 30 years ago,” he said. “If people say you can’t ethically do anything, that we should leave them alone—that produces a neglected group who no one’s really thinking about how we can help. When you look at it from that point of view, it’s a fairly dreadful situation, just in a different way.”

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