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The biological reaction that marijuana triggers in the body had long been a mystery. Scientists could dissect marijuana’s active component — THC — tinker with its structure and conjure synthetic compounds based on that. But they did not know whether THC worked through non-specific interaction with cell membranes or whether it interacted with the brain’s sensory receptors, which read neurochemical messages and tell cells what to do.

Then, in the late 1980s, came the discovery of something called the cannabinoid receptor, which confirmed the latter of the theories. This was the system that THC stimulates. But it was much more than that.

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Its discovery marked a crucial moment in the development of synthetic cannabinoids. Rather than fumbling around in the dark, chemists could aim for a specific target — the cannabinoid receptor. Pioneering researchers started synthesizing fresh compounds to see how the receptor reacted to them.

“It took the black-magic aspect of marijuana’s activity and gave it a biomolecular mechanism in your body,” said Brian F. Thomas, a principal scientist with RTI International, a research institute. “Because you had this cannabinoid receptor, you could then look and find new compounds that can bind to that receptor.”

—Terrence McCoy, writing in the Washington Post about John W. Huffman, a Clemson University chemist who unintentionally helped spawn Washington D.C.’s synthetic drug epidemic. Huffman was the first person to synthesize many of the cannabinoids used in synthetic cannabis. 

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