Notes from the front lines of the 21st century’s Great Mind Experiment.

Fifty years back, there was only one molecule known to be psychoactive in the microgram range: LSD. A microgram is one-millionth of a gram; a small dose is about 150 mcg, so a four-gram sugar cube of LSD would contain roughly 25,000 doses. A chunk the size of a golf ball would be able to keep all the hippies at Woodstock high for days. The fact that LSD is active in such small doses mystified everyone who knew anything about pharmacology, and also made it very scary to people in power.

Today, there are at least a dozen hallucinogens active in the microgram range, and none of them are illegal. They’ve been showing up on the street as “research chemicals,” made in underground labs or more commonly ordered from overseas suppliers via the Internet. Right now, there are only a handful of super-potent synthetics circulating on the street, but in the next few years there may be dozens, even hundreds. There will be too many new chemicals to test on animals, which means they’ll all be tested on human volunteers hoping to find the next great psychedelic or the next “smart drug” to fuel an evolution in human thinking. The 21st century’s Great Mind Experiment is well under way. You may already be a test subject.

Too Much Shit
Ben has one gram of 25-i in a drawer next to his bed. 25-i is a new synthetic hallucinogen that rivals LSD in potency. A strong dose is around 500 mcg, so one gram – barely a thimble of powder – contains well over 2,000 doses. The term “25-i” is another name for 2C-I-NBOMe, 25I-NBOMe, or what the news media call the “N-bomb,” a stupid name that nobody uses. Sometimes it’s referred to as “Smiles,” but people usually just call it “two-five-i,” “25-i” or “the eye” for short.

Ben has more of it than he knows what to do with. I suspect it was ordered over the Internet, but Ben snorts at this suggestion. Maybe he knows a chemist? He won’t say. For obvious reasons, Ben is paranoid. He’s not a drug dealer, but rather a college student with an interest in psychopharmacology. He’s tried 25-i three times – by itself, with a small dose of mushrooms and with a small dose of methoxetamine (a derivative of ketamine) – and now he has another 2,000 or so doses left. He doesn’t want to give it away, sell it, take it again or destroy it. He keeps moving it from hiding place to hiding place, hoping to forget about it. “It’s like a weird magnet,” Ben says. “I always know it’s there. I’m always worrying about what to do with it, that someone will find it. I’ve never had that much craziness all locked up in such a small space. It’s sketching me out.”

Ben is no stranger to weird drugs. He’s tried LSD, mushrooms, mescaline, DMT, MDMA and a variety of other chemicals and hallucinogens. But now he’s worried that taking too much 25-i has made him paranoid. At first, he wasn’t really sure it was the 25-i, but now he’s become obsessed with the idea, so he asks me if it’s possible.

“It’s possible, but hard to say,” I reply. “There is no research on 25-i, not even animal research.” And that, in a nutshell, is the core dilemma of the Great Mind Experiment. “If you have a gram of it in your house,” I say to Ben, “you are the test case in phase one of unregulated human trials. You tell me what the side effects are.” After that, I add, I’ll ask around and let him know if I hear of anyone else with similar symptoms.

I find myself doing the job of a psychiatric researcher because there is no published literature on the long-term effects of repeated 25-i use, and people like Ben have nowhere to turn when the Great Mind Experiment goes off a cliff. They look to Internet resources – chat boards, discussion groups, sites like Erowid.org – and they contact underground writers like myself and Hamilton Morris for help, to see if we’ve heard the rumors of people OD’ing and going crazy, of arms falling off, of a batch of this being mislabeled and sold as that, or asking if a particular drug is being sold on blotter or in nose drops, and so on. “I used to know about every new drug,” Ben says. “I used to try every new drug that came around. But now… ” He blinks and shakes his head, thinking about that gram of 25-i radiating weirdness in his bedroom. “There’s just too much shit. Nobody can do it all.”

The Alphabetamines
Any history of designer psychedelics eventually comes back to Alexander Shulgin, the first chemist to systematically synthesize hundreds of novel psychoactive compounds. All through the late ’80s and early ’90s, Shulgin used a brute-force methodology, working substitution methods like an algorithm, churning out new permutations of existing molecules sometimes as fast as one a day. He then tested each new substance on himself, first in microdoses and then in larger ones, until he could feel some kind of psychoactive effect, and recorded the results.

Shulgin produced two volumes of his research, PiHKAL and TiHKAL, which contained synthesis information on hundreds of new psychoactive compounds with names like 2C-B, 2C-C, 2C-T-7, 2C-E, 5-MeO-AMT, 5-MeO-DMT and so on, leading people in the research-chemical scene to dub them the “alphabet drugs” or “alphabetamines.”

By the turn of the century, the number of alphabet drugs on the street was multiplying. Research-chemical companies were operating openly on the Internet, selling unscheduled drugs as quickly as they could produce them. The authorities were slow but predictable in their response. Typically, new research chemicals are ignored until somebody shows up in an emergency room; then there’s a period of public outrage, a backlash in the media, and the DEA and local authorities move in to ban analog drugs and shut down Internet retailers.

The result is a never-ending game of Whack-a-Mole: They schedule one drug and another pops up. They take out one group of Internet suppliers, and overseas companies or anonymous online marketplaces like Silk Road pick up the traffic. The authorities can try to stifle research, but this is the 21st century – people do their own research and publish the results in open forums, or trade secrets with other chemists at annual psychedelic events like the MAPS conference or Horizons NY, where molecules are sketched on cocktail napkins and synthesis methods are discussed in hushed tones over appetizers. Today’s gearheads are still trading secrets about how to get more horsepower out of their engines; they’re just talking about a whole different kind of engine.

Roflcoptr
“The whole roflcoptr thing spawned a lot of conspiracy theories,” says Hamilton Morris, a well-known writer who covers the drug subculture for Vice magazine. “It seems not so far-fetched to me that the arbitrary renaming of methoxetamine with the nonstandard spelling ‘roflcoptr’ was all some sort of carefully constructed marketing strategy.” Morris is referring to a notorious article in Mixmag that rechristened methoxetamine as “roflcoptr” for the first time and claimed it would make you lose control of your bowels.

Coincidentally, at the same time that the Mixmag article came out, a website selling roflcoptr (which may or may not stand for “Rolling on the Floor Laughing, Crapping, Our Pants Totally Ruined”) opened and started taking thousands of dollars in orders. When contacted by Morris, the operators of the site were savvy enough to have press articles ready for Vice but then immediately went on vacation and refused to respond to follow-up questions.

Morris followed the roflcoptr trail until it went cold, and with good reason: After all, he was the one who first alerted the world to the existence of methoxetamine when he published an interview in Vice with the chemist who’d created it a year earlier. Traditionally, the development of a new drug happens in an academic or research lab, the results are published in a peer-reviewed journal and then years of follow-up study are required before human testing. In the underground, when an amateur chemist creates a derivative of ketamine as an experiment, someone like Morris catches the story and writes it up for Vice, and a new synthetic is born.

Academia is more or less obsolete in this underground model, and trying to catch a new drug evolving in the wild is like a Discovery Channel for the mind. But before the Mixmag and Vice articles, roflcoptr was known as “MXE” in the Bluelight forums, where chemists go to trade esoteric information. MXE was spotted here first, before it escaped into the wild and was turned into the drug that makes you shit your pants. Like a Pokémon, the ketamine offshoot that Hamilton Morris made famous flew away and began reproducing in the wild. Gotta catch ’em all.

Hacking the Shulgin Algorithm
Although the so-called psychedelic effect of hallucinogens on the brain has long been a source of mystery, it is now understood that two serotonin receptors are responsible for the majority of hallucinogenic action: the 5-HT2A and 5-HT2C receptor subtypes. Any drug that promotes activity at these receptors is likely to be hallucinogenic, producing the geometric grids, spirals, floating patterns and rainbows of color associated with tripping.

If one of Shulgin’s molecules hit these receptors, however, it was mainly by accident, since Shulgin had no way to predict or test the receptor affinity of the drugs he produced. But in a lab at the University of Purdue in Indiana, a pharmacology professor named David Nichols spent his career researching psychedelics to find the properties that make them hallucinogenic, and then having his team of grad students synthesize the UFP (or “ultra-fucking-pure”) variations of those drugs for testing in rats trained to recognize hallucinogens.

Many breakthrough technical discoveries came out of Nichols’ lab, but they all essentially boil down to this: Drugs that act as agonists at the serotonin 2A and 2C receptor subtypes are likely to be hallucinogenic; if those drugs have amine tails locked in a specific angle, they are likely to be even more potent; if they have any number of substitutions on their open carbon positions, they are likely to be more potent still because they take longer to metabolize; and if they have certain substitutions on their amine tail – specifically a 2-methoxybenzyl group – they become super-potent like LSD (i.e., active in the microgram range), and their hallucinogenic receptor affinity goes through the roof.

Using Nichols’s discoveries, an amateur chemist can take any one of Shulgin’s hundreds of alphabet molecules like 2C-i, make a simple substitution to the amine tail, and turn it into 25I-NBOMe, a super- potent 5-HT2A agonist active at thousands of doses per gram. Now 25I-NBOMe is passed around on tabs and in droppers as 25-i, even though 25-i doesn’t necessarily imply the NBOMe variant – which can be confusing, but that’s the way drug shorthand naming often works.

25-i is cheaper and simpler to make than LSD. It can likewise be sold on blotter or in nasal drops or spray, and it’s being distributed at parties and festivals around the country right now – sometimes even as LSD. But 25-i is not LSD. It’s a bit speedier and doesn’t last quite as long; also, you have to snort it or hold it in your mouth for it to work, and it has a nasty taste. And 25-i is only one of many NBOMe-based compounds (like 25C-NBOMe and 25E-NBOMe) that have made their way to street-level distribution. These two dozen or so NBOMe compounds are just the beginning, because they’re the simplest to make. But the permutations are endless. There are also hundreds of existing drugs that can be tweaked to become 10 times more potent. These hypothetical drugs are out there waiting to be synthesized by industrious underground chemists; the only thing standing in their way is time and money.

The Froth of White Noise
It has become increasingly difficult to keep track of all the evolving threads of new synthetics. When the overdose deaths of two North Dakota teens and actor Johnny Lewis, a Sons of Anarchy cast member, were blamed on 2C-i in September 2012, police and toxicologists were confused, because 2C-i is not generally known to cause overdoses. Was it really 2C-i, or was it 2C-I-NBOMe, a.k.a. 25-i? In the media confusion, the deaths were blamed on a drug called Smiles, clarifying nothing. A similar thing happened in 2009 when a batch of 2C-B-fly was sold as bromo-dragonfly, a totally different drug, which led to some very unfortunate overdoses. Which makes you wonder: Why are there two drugs named “-fly” in the same class, and isn’t having similar drugs named 2C-i and 25-i a little confusing?

Actually, it can be very confusing, and there’s no way of knowing what’s in the eye dropper, white powder or sheet of blotter going around, no way to know if it was labeled correctly or dissolved and mixed properly. Most people who try 25-i say it’s great – that it has all the hallucinogenic qualities of LSD without being too introspective, offers impressive visual patterns and a great body high, and doesn’t seem to cause lasting problems even in large doses. But there are a few people like Ben who took a bigger dose, got trapped in obsessive loops and became a little paranoid in the aftermath. And a handful of people looking for a good time have overdosed while snorting 25-i or mixing NBOMe chemicals with other drugs. Erowid.org currently has a notice warning people about deaths related to snorting 25-i. The lethal-dose range, or LD 50, for 25-i has not been established, but it’s safe to say there is one, and that it’s far lower than that of LSD.

Overdoses on new synthetics may be chipping away at the image of psychedelics as “safe” drugs for experimentation. Everyone knows it’s almost impossible to overdose on LSD or mushrooms, but recent evidence has shown that 25-i is much less forgiving. The uncertainty over potentially dangerous new chemicals is spreading fear in the underground dance scene, which has seen a shift away from dabbling in super-potent research chemicals and back toward embracing good old MDMA – “ecstasy” when sold in pills, “molly” when sold as powder. At one point, it was impossible to tell what was in those party pills, and all kinds of adulterants crept in, from ketamine to caffeine, ephedrine, meth – you name it. These days, testing kits are available from DanceSafe.org and other harm-reduction groups that will tell you if your pill or powder contains pure MDMA. Or you can send a sample to EcstasyData.org; they’ll test it for you and publish the results online.

Finding pure MDMA is safer and easier than ever before, but unknown compounds like MXE, NBOMe chemicals and alphabet drugs are often too obscure and scary for the recreational user. It’s impossible to keep track of the safe-dosage range for each new drug, and ever-willing test subjects often go into the Great Mind Experiment with the casual bravado of “Let’s see what happens now… ” Usually, the only thing that happens is that everyone has a good time – but any new drug may surprise you. Even the synthetic weed substitutes being sold as Spice or K2 or Potpourri at gas stations can pack a nasty punch, causing hallucinations, rapid heartbeat and panic attacks, leading to emergency-room visits. In many cases, nobody knows what’s in the synthetic pot packets – not the guy selling it, not the toxicologist writing up the overdose report, not the reporters writing the news articles, and especially not the people buying and smoking the product.

The Big Unknown
When I follow up with Ben a few weeks later, he tells me that his paranoia is gone and that he’s been experimenting with tiny doses of 25-i again. He’s taken a small pinch of powder – about 100 doses’ worth – and put it into a solution in a nostril sprayer that can deliver a weak or strong dose depending on the number of pumps. With the pump spray, he can precisely measure the dose, so he isn’t worried about doing too much – but now he’s paranoid that the cap will break and a hundred doses of super-potent psychedelic juice will spill all over the place. He’s also found out that 25-i is still legal in his state, so the paranoia of getting busted has lifted, even though there’s an ongoing federal case to prosecute 25-i under the Federal Analog Act, and it has already been made illegal in four Southeastern states. He says he wants to try 25C-NBOMe next: It’s supposed to be shorter-lasting than 25-i, but much harder to find. Ben puts it on his list of more shit to try.

“This is one of the riskiest, wide-scale health experiments in all of human history,” says Dave Nichols, now retired from the Purdue University lab where he and his grad students tested the “ultra-fucking-pure” 25I-NBOMe compounds on rats. “People contact me and tell me that they really enjoy these compounds, or that a chemical we designed in our lab provided a nice experience, but nobody knows what the long-term effects are. They could cause kidney or liver damage, cancer, or who knows what. It’s just a big unknown.”

While talking to Nichols, I type “buy MDPV” into a search engine and find dozens of sites selling research chemicals, some of which I don’t recognize. I rattle off a list of compounds for sale from a Chinese lab, including AM-2201, 4-FMA and 6-APB. “6-APB is a compound from my lab,” says Nichols with exasperation. He designed 5-APB and 6-APB to test the two oxygen positions in MDA for hallucinogenic receptor affinity, then tested those drugs on rats. When Nichols found that the APBs were hallucinogenic in rat experiments, he published the results. 6-APB never existed before the Nichols lab designed it in 2006 and was never tested on humans, but it has recently been discovered in the wild being sold under the name “Benzo Fury.” It comes complete with a logo, a professionally printed foil package and everything else needed for mass-volume retail sales. Another synthetic evolves, grows wings and takes on a life of its own.

 

[Author’s note: As this story was being filed, the United Kingdom passed an emergency 12-month ban on Benzo Fury and 25I-NBOMe.]

James L. Kent is the author of Psychedelic Information Theory: Shamanism in the Age of Reason and the host of the DoseNation.com podcast.