Russo’s research was not without its problems. Scents could not be totally eliminated, the effects of THC couldn’t be successfully blinded and the prodigious daily cannabis intake of at least one participant made him a poor judge of the effects of individual THC/terpene combinations. Still, Russo found consistent correlations. THC alone, he found, lowered mood and distorted perception, and proved over all to be “really hard to function on.” He recalled one session in which, as it turned out, he had inhaled pure THC. “It was my turn to make dinner that night, and it was like: ‘Oh, God, I’m not sure I can do this. Where’s the knife? What do I need to do next?’ Everything was so hard.” But throw in pinene, the terpene that gives a pine woods its scent, and “all of a sudden that’s gone. You’re clear. You have no problem remembering anything.” Limonene, one source of citrus’s distinctive odor, also cured the THC blues, “making this unpleasant thing vibrant and alive and electric.” On the other hand, some terpenes just made things worse — like myrcene, an oil that smells a little like cloves and is present in high concentrations in hops, on which, Russo recalled, “I can’t function, I can’t think, I can’t move.”
In 2010, at a conference honoring Mechoulam, Russo presented a paper called “Taming THC,” which compiled more than 400 studies that strengthened the case for the role terpenes played in the variable effects of pot. It did not directly mention Russo’s D.I.Y. research, but a careful reader could find observations about the effects of specific combinations on memory, cognition and mood — that myrcene-heavy strains may produce “couchlock,” that pinene might be an “antidote” to the negative effects of THC — that were at least as indebted to Russo’s experiments in Amsterdam as to anything in the scientific literature. The paper was published the following year in the prestigious, widely read British Journal of Pharmacology.
Russo was not the only cannabis researcher studying terpenes, and “Taming THC” was not the first scientific article to speculate about their role in cannabis intoxication. It was also meant to be the starting point for more rigorous research into terpenes, not the final word on their effects. But the article, with its concise charts of correlations between terpenes and drug effects, came along at a crucial moment in the history of pot: By 2011, 15 states had approved medical marijuana, and Colorado and Washington were on the verge of making the drug legal for recreational use.
A new industry was ready to burst into being, and here, in the legitimate academic press, was a paper providing a map to what Russo called a “pharmacological treasure trove.” If the paper’s promises held up, a company could even take aim at the most tempting prize of all: the vast number of Americans who had never tried weed before, and others who had aged out of it but might be brought back on board. For that market, it wasn’t enough for cannabis to be legal; the drug had to be as predictable as a pre-dinner martini.
“Taming THC” laid out an ambitious scientific agenda for anyone seeking to further test the paper’s claims: “high throughput pharmacological screening,” animal experiments to specify mechanisms of action, molecular studies to establish just how terpenes and cannabinoids interact, animal-behavior studies, brain-imaging research and human clinical trials. Nearly a decade later, this agenda, which is modeled on pharmaceutical drug development, remains unfulfilled.
Recently, however, a few companies in the United States and Canada have begun an aggressive investigation into the entourage effect, though they are forgoing many protocols of the pharmaceutical industry. Last year, I met Jon Cooper, the founder of a company called Ebbu, at a co-working space in Denver. Cooper had been toying with the idea of a cannabis start-up ever since Colorado legalized the drug, but he was deterred by his own history with pot. “I’d had some awesome experiences that I wished I could have all the time,” he told me. But he’d also had “some completely horrific experiences that I never ever wanted again.” Cooper says he couldn’t sell something he didn’t believe in; but what if he could figure out how to “capture in a bottle the awesome experience, so every store I walk into, I could get that same experience. Wouldn’t that be amazing?”
A year after Cooper started Ebbu in 2013, he approached Brian Reid, who was running a lab at the University of Colorado’s school of pharmacy, hoping they could collaborate. Reid’s specialty was exactly the “high throughput” screening Russo had called for, in which algorithms are used to quickly determine which potential drugs would interact with which cellular targets. The university’s lawyers, worried about a possible loss of federal funding, nixed the deal, but Reid eventually decided to go to work for Ebbu directly; in 2016, he became its chief science officer.