Visiting the Factories in China Where Synthetic Marijuana Gets Made

In anticipation of the upcoming fourth season of our HBO show, which will premiere February 5 at 11 PM, we are releasing all of season three for free online along with updates to the stories. Today's installment follows up on a dispatch called Synthetic Drug Revolution, which explored how foreign manufacturers create recreational products that often slip through the cracks of US drug law. Watch the episode below:

Synthetic marijuana made for a major American public health scare in 2015. The term, which refers to any chemical that affects the same brain receptors as weed's active ingredient of tetrahydrocannabinol (THC), was all over the headlines for its abuse by homeless people who can obtain it for as little as a dollar, and teenagers who conflate apparent legality with safety. Emergency room visits spiked around the country, with patients exhibiting symptoms ranging from catatonia to something resembling excited delirium.

Although things have cooled off a bit since last summer, synthetic marijuana, often known as "K2" or "Spice," was back in the news last week when New England Patriots player Chandler Jones allegedly smoked some, only to reportedly show up at a Massachusetts police station shirtless before getting hospitalized.

Despite the efforts of regulators, synthetic weed has often been found in corner stores and bodegas around America. But where it originates is a bit murkier. In the VICE on HBO episode Synthetic Drug Revolution, correspondent Hamilton Morris traveled to New Zealand and China to get a first-hand look at the people and facilities behind this new frontier of dangerous, quasi-legal highs.

VICE: I'm really curious as to how synthetic cannabinoids are produced. I've done a lot of reporting on the public health effects but I have no understanding of how they're actually made. Can you walk me through that?
Hamilton Morris: I mean, there's so many different cannabinoids and there's so many different circumstances under which they're produced. In an academic lab, they're produced on a small scale pretty routinely, and that's where most of these synthetic cannabinoids that are used in "spice"-type blends originated—in academic and pharmaceutical research.

With a couple exceptions, the first synthetic cannabinoids to enter widespread use were called naphthoylindoles, and they are synthesized in a two step reaction where 1-napthoyl chloride, or a substituted derivative, acylates an indole and then the indole nitrogen is deprotonated with a strong base like sodium hydride and alkylated with an alkyl halide like bromopentane. A lot of fuss is made about the fact these drugs are produced in Chinese labs, but the issue is not that they come from China—virtually everything is manufactured in China. The issue is that they are sold in blends where users can't predict the strength of what they are ingesting because the law necessitates deceptive labeling.

One of the labs that we visited in China was producing enormous quantities of an intermediate for an experimental antiandrogen designed by the pharmaceutical company Roussel Uclaf. Presumably, it would have no psychoactive effect and was being sold on the grey market to treat androgenic alopecia [a common hair loss condition]. So they're making drugs for baldness, acne, synthetic cannabinoids, antibiotics, ketamine derivatives—all in the same labs. The people that are producing them are not particularly concerned with the end product or who's using it. They're chemists, not moralists.

Right. So when you spoke to those people, were they suspicious of your motives for going there?
I wanted to be honest and say, 'I'm a journalist, but I've also worked in a lab and understand what you do and I'm not here to vilify your work but rather to understand how and why these substances are being manufactured.' But being honest didn't really work and we had an enormous amount of difficulty gaining access.

I'd been to China once before to shoot in cannabinoid labs with VICE in 2012. That time, we posed as buyers from a European legal high reseller and we did get some interesting access, but it wasn't quite enough. When I went back for VICE on HBO, I thought the best way to gain access would be to travel with Matt Bowden. He was already the subject of the piece and he'd poured millions of dollars into the cannabinoid industry in China so I assumed the manufacturers would feel indebted to him. His money had literally built factories in Shanghai.

But even with Matt Bowden and all his clout, the manufacturers still didn't feel comfortable allowing us to film in their labs as journalists. So we reoriented our stated goal slightly—we told the manufacturers that we were using their labs as a location to shoot a steampunk rock opera, and they were totally OK with that. The cannabinoid chemists really loved Matt Bowden's music; they would stop synthesizing cannabinoids to film us on their phones. So we made the HBO piece, but we also shot a great music video for Matt Bowden that I hope will be released soon as well.

Crazy. But did the people there know that they were making chemicals that are designed for abuse overseas? Or did they not even realize it?
I think the actual chemists doing the benchwork in many instances did not know. The synthetic cannabinoids aren't being sold or used domestically in China and the chemists certainly weren't using the drugs themselves, so if they did know, it was in some very abstract capacity. The people that owned the labs who were overseeing the business end had a better idea, but even they may not fully understand beyond the market demand.

There was one lab we visited that was doing contract work for Pfizer, and I asked them if they could offer a chemical called MDMB-FUBINACA that had been implicated in a lot of deaths in Russia, and the chemist that was working there scolded me for even asking about it because she was following the news and was aware that it had been implicated in these fatal poisonings. So that was a definite exception—she knew how the compounds were being used and had concerns about their toxicity.

Did you get a sense of how many people were working in the facilities you visited or how much output they were responsible for?
We went to about a half-dozen labs. There were different scales, different degrees of technological sophistication. I imagine there are over a thousand labs producing these substances in China now. It's almost entirely cannabinoid oriented, [but] maybe in the future that will change. All the labs could produce kilogram quantities of cannabinoids active at doses below one milligram; some of them could have produced hundreds of kilograms.

Do you have any sense of how these substances get from these facilities in China to the corner store in Brooklyn? What happens between those two steps?
The pure chemicals are purchased in bulk, then they're dissolved in a solvent like acetone, the acetone-cannabinoid solution is poured over an inert plant carrier, generally damiana, and the acetone is evaporated, leaving a cannabinoid-impregnated leaf that's stuffed into foil envelopes and sold. The profit margin is enormous. Often the amount of chemical in one of these packets that sells for $15 would be a small fraction of a dollar, if not a fraction of a cent.

Oh wow, okay. I know these drugs have been around for a long time, but it was really only last year when we started hearing about a huge spike in emergency room visits. Is there a second generation of chemicals that's more dangerous than the ones that were first banned by the feds, or is there another explanation as to why we're seeing this all over the news?
There are so many social factors that go into a drug's toxicity—the direct biological effect is only part of the equation. With synthetic cannabinoids, I think the primary issue is not necessarily the drugs themselves but the fact that they are sold as mixtures with unknown potency and deceptive labeling, which is necessitated by prohibition. It's not something the manufacturers do out of malicious intent.

Of course, it's not ideal to introduce a drug that has never been used outside an in-vitro binding assay into a population of thousands of humans, but this is an industry created by prohibition, and many users choose synthetic cannabinoids because they are being drug tested or because they can't afford Cannabis. As soon as one synthetic cannabinoid becomes familiar, it's prohibited and a new one is introduced to take its place and this constant influx of new drugs dramatically increases the chance of people encountering one that really does have unacceptable toxicity.

Also, despite the endless scare stories in the media, I think many people are still skeptical that synthetic cannabinoids really do get you as high or much higher than Cannabis. They might buy a packet at a bodega and think that there's no way that this stuff—this potpourri—could be as strong as weed, when in fact it could be a hundred times stronger.

Synthetic weed can make people freak out, but it also can make people become comatose. So is there an explanation as to why the reaction varies so wildly? Is it based on which cannabinoid happens to be used?
Some synthetic cannabinoids have been known to cause seizures or a sort of excited delirium in certain users, and some have been known to decrease blood pressure to the point that users lose consciousness and asphyxiate on their own vomit. Virtually all of these cannabinoids bind to the CB1 receptor in the brain, but beyond that there are enormous variations in potency, functional activity, off-target binding, and an enormously diverse population of users taking different doses often in combination with other drugs. In Japan, there was a trend for some time of selling synthetic cannabinoids with NMDA antagonists like diphenidine or methoxphenidine; then you're dealing with interactions between drugs that are already unknown in isolation. It all paints a very complex toxicological picture.

How many varieties of synthetic cannabinoids could exist? Is the DEA's method of banning several at a time practical or not given that there are millions of permutations?
Not only is it completely impractical, it's extremely unsafe. Prohibition has been terrible at achieving its goal of preventing people from using psychoactive drugs, and it's maximizing the harm for users. Every time a drug comes out that people enjoy, the first response is to make it illegal, to take it off the market so that it has to be replaced with something that is relatively unknown and could be much more toxic. If Cannabis were federally legal, people wouldn't be using synthetic cannabinoids. Even within the realm of synthetic cannabinoids, the first generation synthetic cannabinoids that came out around 2009 like cannabicyclohexanol and JWH-073 were relatively benign and well tolerated, but they were prohibited and it eventually lead to compounds like MDMB-FUBINACA that have a very narrow safety margin.

The number of possible cannabinoids is near infinite. From the beginning, I knew there would be hundreds possible, and years later I'm still surprised every month when I see the array of new structures appearing on the market.

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