A Young Chemist Explains How Legal Highs Work

Image via Wikicommons

As long as there are governments that don't want young people to go around indiscriminately hoovering up drugs, there will be chemists tirelessly working to create new ones that haven't been declared illegal yet.

Research chemicals, or RCs, are often sold as legal highs. They are drugs whose chemical formulas have been altered just enough so that they're not illegal according to analogue laws, which make entire groups of drug illegal because they're checmially similar to a known narcotic. So you take an illegal drug, switch a couple of molecules around, and—presto!—it's a different drug that theoretically will no longer get you in trouble with the police.

RCs are often developed by government-funded projects for medical research. But the formulas for these drugs are published in publicly available scientific journals and seen by people looking to make a quick buck. They go on to mass-produce the new drugs in labs and sell them to people who want to get out of their minds for fun. Unfortunately, because they're altered, people are never quite sure what they are and what effects they will have, which can make them pretty dangerous.

I got in touch with my friend Mathias, who's been developing and synthesizing RCs based on 2C-B as part of his masters thesis to find out exactly how dangerous these new drugs are.

VICE: Hey, Mathias. What's up?
Mathias: Not much. I just finished my thesis, so right now I'm in job limbo.

What was your thesis on?
Synthesis of potentially selective 5-HT2A agonists.

You're going to need to dumb that down for me.
Pretty much all hallucinogens, like mescaline and LSD, have something in common, namely that they activate a protein in the brain called the 5-HT2A receptor [a serotonin receptor] along with several other similar proteins. What I've been doing is trying to make new chemical compounds that only activate 5-HT2A, to maybe tell us a bit more about what this protein does and how it works, because it's obvious that this particular protein is quite important in processing sensory information and emotions.

Think of the 5-HT2A protein as a lock, that can be opened by numerous keys. We're trying to make the best key for that particular lock.

The chemical equation for 2C-B. Image via Wikicommons.

So what, you are developing new forms of narcotics?
Well, that's one way of putting it. I worked with the chemical “skeleton” of 2C-B, a synthetic hallucinogen, making small alterations to the chemical structure. The ultimate goal would be to make a drug without the psychedelic properties of the hallucinogens but with the self-insight and mood changes. However, we generally only test the compounds on the protein itself to see whether they actually activate it and how “well” they do it, so it's hard to say how they actually work with humans.

Recent studies in the US have actually shown that drugs like MDMA, which isn’t technically a hallucinogen, could potentially be used in conjunction with psychotherapy to treat conditions like PTSD. They have also found that psilocybin, which definitely is a hallucinogen, might reduce death anxiety in terminally ill patients. I don't think the compounds I made during my project would be particularly good as drugs in psychotherapy, but then again, nobody knows. The correlation between chemical structure and activity is a bit of a hit-and-miss process at the moment.

So these are published in scientific journals?
Yes. A PhD student I worked alongside with just published an article about how a new class of drugs—the NBOMe class—might be metabolized in the body. That came about because some of these drugs found their way to the gray market and a lot of people who tried them wrote on internet forums that they weren’t active if you swallowed them. Instead it should be ingested sublingually, meaning you have to place it under your tongue.

How do these types of drugs end up on the gray market then?
We make compounds to learn about the brain and to maybe discover new types of medicine. We don't think, This would be a wonderful drug to take when we're making them. Somewhere along the line, some guy with access to a lab sees some scientific article about a new, interesting class of compounds that has some effect on the body similar to a recreational drug, and he realizes that this particular class is not yet illegal. If he can make a huge batch of this before it's made illegal, then he could potentially make a lot of money selling it as incense or bath salts or something innocuous like that.

Where is this stuff made?
That's impossible to say. The best guess would be somewhere without strict laws on recreational drugs. It's then moved into Europe and distributed around the world.

So why are these research chemicals so dangerous?
First of all, only a fraction of them have ever undergone toxicological tests in any animal, including humans. Most of the people selling these compounds don’t really have an interest in the safety of their clients. On the products, they write that it's not for human consumption, so technically they are in the clear if someone drops dead. I know that some of the research chemical vendors have expressed an interest in performing toxicological tests, but those could cost millions of dollars, so I'm not sure how seriously it has been taken.

What's the current trend in RCs?
Besides a lot of chemical variations of amphetamines and cannabinoids, some new classes of hallucinogens have made it into the wild. The group I mentioned earlier, the NBOMe group, was found to activate 5-HT2A selectively and quite potently. They are generally easy to make from the parent phenethylamine compounds—like 2C-B or 2C-T-2—so in a simple chemical process, you can increase the potency by several magnitudes.

For researchers this was extremely interesting, but for the chemists supplying the gray market, it could be a way of increasing income. Just stick on some carbon, hydrogen, and oxygen to 2C-B, and voilà: You have a completely new, more potent drug which could circumvent some analog laws.

Image via Wikicommons.JPG).

So if you had a batch of drugs worth $80,000 you could simply go through this chemical process and end up with drugs worth $800,000?
In theory, yes. I wouldn't put it like that; I don’t know if hallucinogens are the biggest moneymakers, but that's the gist of it. You can vary the specific chemical structure almost indefinitely by changing the formula a little bit. But as a scientist and someone with a bit of common sense, I would never recommend actually using recreational drugs, and especially not research chemicals. Nobody knows what they can do in the body.

There have already been deaths caused by the NBOMe group—something that hasn’t been reported with phenethylamines like 2C-B as far as I know. We don’t really know exactly how these people die. Some people have a certain reaction, almost like a psychotic episode, and then they die.

Pharmacologists talk about something called the "therapeutic window." How much do you need to take for the drug have an effect, and how much does it take to have adverse effects and, in turn, overdose? These new compounds seem to have a very small window. For one because they're so potent, active in micro- or milligram scale, and thus seem to be quite easy to overdose on. Anecdotal claims from some people who have used them, say that they are also somewhat boring drugs to take. Sure, the walls get a bit wobbly and the colors change, but there's none of the insight that you get from LSD or mushrooms. This, of course, varies from person to person, but I don't think it's the best drug class for use in therapy.

What is then?
What I find really interesting is psilocybin [the psychadelic compound found in magic mushrooms]. It’s been proven to be quite safe to use, it only lasts a couple of hours and its potential use in psychotherapy is being investigated. The problem is that it also works on other proteins besides 5-HT2A, and we are generally looking for something that works specifically on the target to avoid side effects.

Is it safer to take classic drugs?
Technically, yes. Psilocybin-containing mushrooms have been assessed to be one of the safest recreational drugs. There's basically no addiction, you can't really overdose, and we know what it does in the body, due to decades of research. Yes, bad trips are known to occur, but the realistic bad trip would basically involve hiding under the covers for a couple of hours—not jumping in front of a bus because you think you’re Superman.

We don't know how the body reacts to the new drug classes. Even small chemical variations of known drugs can drastically change how they are processed in the body. Take Spice, the cannabis substitute which was actually shown to contain synthetically-made compounds that worked on the same receptors in the brain as THC. Even if it chemically doesn't look much like THC at all, I don’t think anyone who ever smoked Spice would really describe the experience as pleasant.

In general, most of the well-known classes of hallucinogens are relatively safe if you take precautions. Although they have been somewhat ostracized in medicine for some time, the newfound interest could potentially be of great worth to the treatment of a variety of psychological disorders. But we still need that one golden key that only unlocks 5-HT2A.