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Is It a Myth That LSD Can Permanently Fry Your Brain?

Pharmacologist David Nichols told me that permanent acid trips make no medical sense.

Mike Pearl

Mike Pearl

When I was 12, Dan, the kid at my middle school who already claimed to have done acid, told me about this guy one town over who had dropped so much acid, he just never stopped tripping. I took it as a serious admonition: Watch your dosage, or you can end up a vegetable, or at least a burnout. Dan used the really unappealing word "frying" to mean "tripping," and he said this guy was "permafried." 

It turns out other people use the term "permafried," too. Drug-education YouTuber NeuroSoup tosses out the term in her video on the subject. Redditors who love acid fear that their favorite chemical could leave them permafried as well, and they cite rumors similar to the ones I've heard. Apparently, there are people out there who did acid once, and "are still kind of gone," one Redditor writes. You may also recall something similar happening to Devon Sawa's character in SLC Punk!, so the rumor is pretty widespread.

LSD users experience what they think is a permanent trip, and there's even a diagnosis: "hallucinogen persisting perception disorder (HPPD)," that shows up occasionally in medical literature. HPPD reportedly causes sufferers to report seeing tracers, after-images, and mild imaginary light shows, along with non-visual symptoms like anxiety. But as Dorian Rolston of the New Yorker pointed out in 2013, other conditions can cause people to "misperceive their environment," and researchers think such "misperceptions" that set in after a super long trip could be mistaken for some kind of mental damage done by the drug.

paper published last week in the journal Cell may illuminate the limits of those trips. LSD is not a drug like alcohol, which only affects you when it's in your blood, and then gets promptly cleared out and metabolized by your liver. According to this latest research—which required the scientists to make radioactive LSD—it turns out LSD doesn't care if it's in your blood at all. Long after acid is purged from your blood, it can hang around on the serotonin receptors in a specific part of the brain called the claustrum—sometimes called the "conductor" of your consciousness—for multiple days. 

"What we basically found out in this paper is that LSD gets trapped in the receptor. But it doesn't stay there forever. It stays for six or seven hours."—Dr. David Nichols

I wanted to know if this meant being permafried is real, so I asked Dr. David Nichols, emeritus professor of pharmacology at Purdue University, and the guy who created the LSD used in the recent experiment. He told me all about LSD's stickiness—what it means for recreational users, and what the limits of that stickiness are. Long story short: You probably don't need to worry about tripping for all of eternity. Nichols also had some potential good news about microdosing.

VICE: This study shows that acid sticks in people's serotonin receptors, maybe for days at a time. Can it stay in there forever and make people "permafried"?
David Nichols: It's pretty much a myth, [but] there are certain people who have a predisposition to certain types of mental illness—schizophrenia is the most commonly known one—those people will eventually develop schizophrenia. It hits you in your late teens and early 20s. So any kind of stressful event will cause the onset of that disorder. It's a developmental disorder, in the development of the cortex. So a lot of kids, they go off to college, and in that first semester, you're diagnosed with schizophrenia. Students [normally] have to go home because it's the stress, but they were primed for [schizophrenia]. Well, people who are primed for it, if they take a lot of LSD, it can trigger the onset of actual psychosis.

Yeah, but what if I take a really, really big dose?
In most circles, if you're mentally healthy, and you're not predisposed to psychosis, then you'll survive those big doses. I've talked to people who have taken massive doses of LSD, and they'll say, "I was high for a week, but then I came back. I thought I was going crazy, but then I came back." People who are not predisposed to mental illness basically survive those types of things. The people who are casualties are people who had a predisposition in the beginning. Probably any dose would have pushed them over the edge. That's sort of the current thinking.

But there is a diagnosis called hallucinogen persisting perception disorder. Can that be the same thing as being permafried?
HPPD is a fairly rare phenomenon. It is described as the presentation of visual effects—like the effects of LSD—but long after the drug has left the body. It has no well-defined treatment, although there are two case reports treating it with an anti-seizure drug. So, my personal speculation is—not proven—that the visual system has become sensitized somehow, and HPPD perhaps represents seizure activity in the visual cortex. 

When you say "the visual system has become sensitized somehow," can that be from acid?
There is no LSD in there. LSD activates serotonin neurons, and normally there are mechanisms to keep them from becoming too excited, so maybe if those don't work, the neurons stay too excitable. No one knows why HPPD occurs, just as no one knows why people get seizure disorders.

In any case, you found that a big dose can make someone trip for a week—even if it can't mess people up for life. How much do you have to take to trip for a week?
You'd need to take 2,000 to 3,000 micrograms, and the standard dose is 100. People talk about pressing your thumb down on powder LSD and licking it—God knows how much that is. Those are unbelievable experiences. In scientific circles, there was the suggestion that LSD might produce some kind of catalytic process because if you looked at blood plasma concentrations of LSD, they were gone, and yet the trip was still going on. No one could ever figure that out—why it lasted so long. What we basically found out in this paper is that LSD gets trapped in the receptor. But it doesn't stay there forever. It stays for six or seven hours. But it stays there long after the plasma concentrations have dropped off.

How special is LSD in this regard?
This is unusual. Not a lot of drugs have been studied to see how many of them this happens with. There are probably a lot of drugs like that—where the length of time it gets locked into the receptor is longer. People generally just don't look for that. It's kind of a hard experiment to do, [so] we were pretty lucky that LSD came in radioactive forms. Otherwise, we wouldn't have been able to do that. 

In layman's terms, what's going on with the receptors when the LSD molecules stick to them?
When they get locked in there and stay for a long time, they start generating a different kind of signal because now the receptor is trying to get rid of it. It doesn't want to be stimulated that long, so it will internalize it or desensitize it. The other things that happen when a substance gets in and stays that long is it changes the quality of the signaling side of the cell. 

So once the LSD is in there, and it's stuck to the receptor, there's no chance that it stays forever? Or damages it?
No. It has to get back out of the receptor to be metabolized by the liver, so it's almost like you would get this depot of LSD and receptors in it, and then it's slowly leaking back out and metabolized. But it doesn't damage the receptor per se. It doesn't interact with it in a covalent way. It doesn't form bonds with it. It's like closing a door over a box, and it can't get out until the lid opens briefly, and some of it escapes. Then when the lid is closed you've got more of it still in there generating a signal. 

Since the drug stays in the brain so long, might that be evidence that microdosing with LSD is a real thing?
I've heard people say, "Oh, talk about microdosing psilocybin, or microdosing some other psychedelic," and LSD is probably the only one that [microdosing] could conceivably work with, assuming it does work, because of this idea of LSD molecules slowly getting trapped in there and staying. Only a fraction of them say that some of them will be occupied with a microdosing. Say you take only ten grams instead of 100, you have 10 percent the amount there, but it gets caught in there and stays and generates some kind of a signal.

So even though there's no clinical trial to tell us anything for certain, this validates the theory, in some regards?
Yeah, it would explain why. 

This conversation has been edited for clarity.

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