Fake Weed Leads to a Real Drug Crisis

Even as states across the U.S. relax laws governing real marijuana, synthetic cannabinoids—commonly known as fake weed, spice or K2—have become increasingly difficult to control. So far this year more than 5,300 incidents involving the drugs have been reported to U.S. poison control offices. That’s more than double the number of calls in all of 2013, according to the American Association of Poison Control Centers. Health departments from Alabama to New York State have issued alerts after a wave of emergencies with the drugs. In New York alone the drugs caused more than visits from April to June.

Users smoke or inhale synthetic pot through vaporizers, and the resulting high roughly mimics the effects of marijuana but with much harsher side effects, including heart attacks, strokes and kidney damage. Synthetic drug users also sometimes become so delusional and violent that restraining them requires multiple people and the use of antipsychotics.

Producers of the drug use a continually rotating list of ingredients. And each time the federal government places a compound on its schedule of illegal substances, the suppliers replace that chemical with a new one. These ever-shifting recipes make it hard for researchers to identify new drug formulations and link them to their side effects.

Marilyn Huestis, chief of the Chemistry and Drug Metabolism Section at the National Institute on Drug Abuse, spoke with about the history of these drugs, what researchers know about them and how they can affect the brain.

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How do synthetic cannabinoids work in the brain?

Where do synthetic cannabinoids come from?

How do these drugs resemble pot

Also of concern are the crash effects: After using cannabis people tend to get sleepy, but coming off a high with synthetic cannabinoids, there is a lot of sleepiness. We have seen problems with people driving impaired—people have stopped in the fast lane of the highway. There is also a lot more violence and aggression with these drugs than you would normally see with marijuana. Some of these synthetic cannabinoids have caused severe kidney damage, too, and that’s something we don’t tend to see much with users of cannabis.

Who is making the compounds now?

Federal officials have placed some of the drug’s ingredients on their most restrictive list of illegal substances (Schedule I), and that has prompted drugmakers to find substitutes for those ingredients. How do the drugs still get people high?

Basically, you spray chemicals over any kind of plant material. The plant materials themselves actually may have activity themselves and the user never knows that. You really don’t know what you are getting at all.

What are researchers doing to help identify these drugs?

We don’t have the basic toxicology data we need. We don’t know how these drugs affect people or even how they affect animals. We want to do those studies but haven’t been able to do them yet, partly because we don’t have the basic data [the U.S. Food and Drug Administration] would require for testing them in human volunteers. The other issue is funding.

What our plan is, and I’m still hoping we can do this eventually, is to take one of these drugs—one that does not cause heart attacks or kidney failure—and study how it affects humans and then compare all the other versions in the future to that one, comparing how they bind to CB1 and CB2 receptors.

How do you identify new versions

We have a partnership with the DEA, and as soon as they start seeing seizures they provide the drug to us. We use human liver hepatocytes that metabolize the drug like the liver does. We feed the drug to them and identify metabolites from that process. Once we identify metabolites we can say these are the top three or five metabolites you will find with this drug so please make these standard [for law enforcement drug tests].

Separately, part of our testing is identifying the half-life of the drug. Most of these compounds have short half-lives, but if it has a long half-life, then we worry about a lot more about potential interactions with other drugs or medications and even over-the-counter supplements they might be taking. 

Where are you with research now

It’s become obvious we can’t keep up with the release of all these new chemicals, so now my lab has done a lot of work with high-resolution mass spectrometry. We capture all ions present in a single sample and then analyze what metabolites are present. It’s very analytically challenging but it enables us to look for metabolites that we don’t yet know are produced [in the new formulations]. This kind of nontargeted mass spectrometry has a huge learning curve but I think this is where the field has to go. We can’t keep up with the new drugs that are coming on the market, and I think this is our only hope.

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