Rewiring the Brain Without the Reckoning

Eli Lilly, the Big Pharma player that introduced Prozac to the world, just spent up to $3.8 billion to move into psychedelics. The main drug in the deal—a manufactured form of 5-MeO-DMT, a psychedelic found in the venom of the Sonoran Desert Toad—is a chemical cousin of the compound psilocybin found in magic mushrooms, often used to treat depression when all else has failed. Of interest, in the announcement, Lilly avoided using the word psychedelic. Instead, in a clinical-sounding term borrowed from the lab, it called the drug a rapid-acting neuroplastogen, which merits a closer look.

Neuroplasticity is the brain’s ability to rewire itself and to grow new connections between cells. The theory behind these drugs is that the state of being depressed leaves certain brain circuits stuck, and a psychedelic is able to pry open a temporary window in which the brain is able to rebuild those circuits. In the industry’s clever coinage, a “neuroplastogen” is a compound similar to psilocybin that also opens that window. And the addition of the words “rapid-acting” means the drug is promoted as working in hours.

It is critical to note what the term neuroplastogen leaves out regarding the term psychedelic. In the therapy behind this field, the drug does not work quietly in the background. In a quiet setting, the patient often goes somewhere for hours, spending time inside their own mind, meeting old wounds, crying, and usually feeling connected to something much larger. Indeed, many undergo what they later describe as one of the most meaningful events of their lives. Eli Lilly and the word neuroplastogen mention none of those things. Instead, it moves the healing out of the mind and into the brain tissue itself, feelings be damned. The drug purchased by Eli Lilly still produces the journey, hours of it. But the company refuses to name it, instead calling the experience a side effect rather than the cure. Hmm, once the experience becomes incidental, then why not do the next thing? Such as shortening it, dampening it, and eventually building a version with no experience at all? Don’t think that won’t happen, because researchers are already trying it.

But hold on. Whether the experience is incidental is not a settled fact. It is a bet on one side of a real, and unfinished argument, and a great deal rides on who wins it.

On one side is a chemist named David Olson, who coined the term “psychoplastogen” (the industry uses “neuroplastogen”). His life’s work is designing psychedelic molecules that trigger the rewiring of the brain while removing the trip. In other words, a psychedelic with the psychedelia engineered out. Olson’s evidence relies on mice, which show brain changes and improved behavior, as if they are less depressed. And the mice, presumably, are not having an internal revelation during the experience. Thus, Olson’s camp reasons that the experience must be incidental.

On the other side is Johns Hopkins scientist, the late Roland Griffiths, who studied these drugs in people for decades, and who answered Olson with a paper with a title that simply reversed his, insisting the experience is indeed necessary. Griffiths’ evidence came from humans and pointed the other way. Again and again, the depth of the experience, according to Griffiths, predicts how much the patient improves.

Then researchers ran the test directly, giving individuals psilocybin alongside a sedative that let the trip happen, but erased the memory of it afterward. Sounds straight out of science fiction. What happened? When the memory was gone, researchers noted that much of the benefit seemed to fade. And this was not the only such test. At Stanford, researchers gave depressed surgical patients ketamine, a cousin of these drugs, while they were already unconscious under anesthesia, so they missed the experience entirely. It worked no better than salt water. The experience, in these early but pointed studies, was not an unnecessary side effect. It was doing crucial work. It is important to highlight that experiment: scientists built the bypass on purpose—a way to have the healing event without remembering it—and the healing seemed to fade away.

Undoubtedly, the science here is not closed. The mouse studies cut both ways, and a mouse cannot tell anyone what it felt, regardless. Likewise, the results are mixed in people, too. One study found the best predictor of relief was simply how relaxed the patient was, not how mystical their experience was. No studies have landed the final proof, but that should be the point here. The question is open, with evidence tilting toward the experience being crucial. Yet, Big Pharma has committed to the opposite answer, not because science demanded it, but because it is the answer they can profit from—a pattern we have seen repeatedly.

If the experience really is disposable, then in principle, it would be possible to reach into a person and lift out their trauma, their grief, an addiction, and so on, all without them having to pass through anything emotional at all. No reckoning. No internal cleansing. No insight. Nothing. Instead, a person goes in stuck and comes out unstuck, and the hours in between are manipulated down to nothing. This is the future that the word neuroplastogen quietly points toward, and Eli Lilly’s deal is the first time that idea gets a multibillion-dollar foothold in traditional medicine.

Part of that bypass is mercy, and that part should be plainly highlighted. Indeed, some suffering carries no lesson worth the price of learning it. The veteran trapped in one afternoon, the survivor whose body fires at a smell, both held hostage by the involuntary, physical nature of their trauma. Likewise, the person whose depression has no trauma to reckon with. For them, relief without reliving the worst hours of their life is not a loss. It is a gift. The long-supervised journey through that trauma is itself brutal, and it shuts out the fragile and the poor. A treatment that skips the ordeal could genuinely help certain people. No argument there.

And yet. Our human experiences, even the most unbearable ones, are load bearing. Grief is the shape love leaves. Fear after harm is memory doing its job. If the weight of an experience can be edited without the person having to live and heal through it, we are no longer just treating an illness. We are editing a self. We are editing a human being. Who decides which experiences are disposable, and by what standard? These questions are not raised in a press release. Yes, grief is painful and can get in the way of work. But is it a disorder to be dissolved? Guilt is unpleasant, but do we edit that too? Think of the ramifications. Once the tool exists, the line is drawn by whoever owns it. And in this case, that is whoever stands to profit.